Volume 31,Issue 5,2022 Table of Contents

1 Clinical application of inverted T-incision and axial three-pedicle breast reduction in the treatment of moderate to severe breast hypertrophy and macromastia

LI Juan , FENG Yu , ZHANG Donglin , LIU Fang , LIU Zhenfang , ZHOU Jiao , QIN Xiangquan , LIU Xinran , QIU Mengxue , YANG Huanzuo , DU Zhenggui

2022, 31(5):559-568. DOI: 10.7659/j.issn.1005-6947.2022.05.001

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Background and Aims Reduction mammaplasty (breast reduction surgery) is effective method for the treatment of breast hypertrophy and macromastia. There are a variety of surgical options for breast reduction, and the principal criteria for surgical success are the preservation of blood supply and sensation of the nipple-areola complex (NAC) as well as satisfactory postoperative breast appearance. The authors' team previously developed an axial three-pedicle breast reduction technique based on an inverted T-incision, and satisfactory results were obtained in breast cancer patients with concomitant breast hyperytophy and/or moderate to severe breast ptosis. This study was performed further evaluate the application efficacy of this method in patients with moderate to severe physiological breast hypertrophy or macromastia.Methods The clinical data of patients with moderate to severe breast hypertrophy or macromastia who underwent inverted-T incision and axial three-pedicle breast reduction between January 2017 and March 2021 in the Department of Breast Surgery, West China Hospital of Sichuan University, Fourth People's Hospital of Sichuan University and Longquan Branch of West China, Sichuan University were collected. The incidence of postoperative complications (NAC necrosis, T-incision dehiscence, cellulitis, hemorrhage, skin flap necrosis, and fat liquefaction) was recorded. The treatment outcomes were determined by self-assessment of the breast satisfaction, physical well-being, psychosocial well-being and sexual well-being of the patients in the BREAST-Q reduction/mastopexy module before and after breast reduction.Results A total of 28 patients (53 breasts) were included. Of the patients, the average age was (33.7±6.8) years old, and the average BMI was (25.8±3.2) kg/m². The breast cup size was E in 2 cases, FF in 2 cases, G in 4 cases, GG in 7 cases and H in 13 cases before operation. The average tissue resection weight for the left and right breast was 993.5 g and 1 017.7 g, and the elevation distance for the left and right nipple was (14.4±3.7) cm and (14.5±3.4) cm, respectively. After the operation, the breast cup size was B in 10 cases, C in 15 cases, and D in 3 cases. The overall incidence of postoperative complications was 7.5%. T-shaped junction wound dehiscence occurred in one case, and breast cellulitis and fat liquefaction occurred in one case each. The NAC was preserved in all patients, and only 1 patient (1.9%) developed hypopigmentation of the NAC. The median follow-up time was 24 (1-36) months. The preoperative breast satisfaction score was 15.5±8.2. The postoperative breast satisfaction scores at 1, 3, 6 months, and 1, 2 and 3 years after operation were 32.2±4.8, 42.6±7.5, 52.7±8.0, 52.7±8.5, 56.9±8.0 and 60.8±5.1, respectively, which were all significantly higher than the preoperative score (all P<0.05). The postoperative scores of psychosocial well-being and physiological function at each time point were significantly higher than those before operation (all P<0.05). Except for the first month after operation, the scores of sexual and physiological well-being at the remaining time points were significantly higher than those before operation (all P<0.05).Conclusion For patients with moderate to severe breast hypertrophy or macromastia, the inverted T-incision and axial three-pedicle breast reduction is an ideal procedure, with simultaneous advantages of good cosmetic effect and relatively less complications.

2 Nipple-areola-complex sparing mastectomy with one-stage reconstruction using prosthesis and TiLoop Bra versus oncoplastic breast-conserving surgery for breast cancer: a single center retrospective study

XIAO Zhi , DING Nianhua , CHEN Feiyu , HUANG Juan , WANG Shouman

2022, 31(5):569-576. DOI: 10.7659/j.issn.1005-6947.2022.05.002

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Background and Aims The age of onset of breast cancer in Chinses women is relatively young, so breast-conserving surgery and breast reconstruction following mastectomy are reasonable options to correct breast volume loss in breast cancer patients. With the promotion of breast oncoplastic surgery in recent years, a satisfactory breast shape can be maintained in patients with small-sized breasts after breast-conserving surgery. The breast reconstruction technique using prosthesis combined with a titanium mesh (TiLoop Bra) is relatively simple and easy to popularize, and can also effectively restore the breast shape after total mastectomy. This study was performed to evaluate the pros and cons of the two approaches in terms of surgical efficacy and meeting the functional and cosmetic requirements of patients, so as to provide information for clinical decision-making.Methods The clinical data of patients with early breast cancer undergoing above two procedures from January 2019 to October 2021 in Department of Breast Surgery, Xiangya Hospital, Central South University were retrospectively analyzed. Of the patients, 40 cases each underwent oncoplastic breast-conserving surgery (breast-conserving group) and nipple-areola-complex sparing mastectomy with one-stage reconstruction using prosthesis and mesh (breast reconstruction group). The basic clinicopathologic information of the patients, duration of operative time and drainage after operation, length of postoperative hospital stay, hospitalization cost and the related complications were collected. The outcomes of breast surgery and and patients' satisfaction with their breasts were assessed using the Breast-Q questionnaire.Results Breast-conserving group was significantly superior to breast reconstruction group in terms of operative time, postoperative drainage time, and postoperative hospitalization time and cost (all P<0.001). The incidence rate of nipple numbness in breast reconstruction group was significantly higher than that in breast-conserving group (P<0.001); skin flap necrosis occurred in 4 cases in breast reconstruction group while in none in breast-conserving group, but the difference did not reach a statistical significance (P=0.079); no significant differences were noted in incidence rates of hematoma, infection, fat necrosis and tissue contracture between the two groups (all P>0.05). There were no significant differences between the two groups in mental health, physical health and sexual health as well as the degree of subjective satisfaction from the patients for their breast shape (all P>0.05).Conclusion The two surgical approaches have a similar aesthetic effect. Skin flap necrosis is a serious complication in breast reconstruction with prosthesis and mesh, for which latissimus dorsi myocutaneous flap can be used as a remedial treatment. Breast-conserving surgery should be preferentially considered in patients who meet the indications. Nipple-areola-complex sparing mastectomy with one-stage reconstruction using prosthesis and mesh is an alternative option after reasonable evaluation for those with contraindications to breast-conserving surgery but with a requirement for the appearance of the breast.

3 Clinical application of oncoplastic technique in breast-conserving surgery for breast cancer

SHEN Yuhou , YUE Aimin , YIN Hongda , JU Andong , GUO Junqiang , QI Pan

2022, 31(5):577-586. DOI: 10.7659/j.issn.1005-6947.2022.05.003

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Background and Aims Oncoplastic breast-conserving surgery (OBCS) allows complete excision of tumors while maximally maintaining the natural breast contours, thereby improving the patients' quality of life. However, OBCS is a newly emerging technique, the clinical evidence of its efficacy and safety is still limited. Therefore, this study was conducted to further determine the clinical efficacy and safety of OBCS through comparing the relevant clinical variables between OBCS and traditional breast-conserving surgery (TBCS) in the treratment of early breast cancer.Methods The clinical data and follow-up records of 226 patients who underwent breast-conserving surgery for breast cancer in the Department of Oncology Surgery of Xinxiang Central Hospital from January 2015 to January 2020 were retrospectively analyzed. Of the patients, 95 cases underwent OBCS (OBCS group) and 131 cases were subjected to TBCS (TBCS group). The clinical variables that included the operation-related indexes, incidence of postoperative complications, postoperative cosmetic outcomes, patients' subjective satisfaction and long-term efficacy between the two groups of patients were compared and evaluated.Results In OBCS group, the defect closure methods included glandular advancement in 47 cases, transposition flap placement in 22 cases, inverted-T mammoplasty in 5 cases, bat-wing technique in 9 cases, pedicled omental flap reconstruction in 3 cases, partial latissimus dorsi added fat flap reconstruction in 3 cases, latissimus dorsi flap reconstruction in 4 cases, and rectus abdominis flap transposition in 2 cases. In TBCS group, the extended local excision of the tumor was performed in all patients, followed by direct residual gland suture. The operative time in OBCS group was significantly longer than that in OBCS group [(136.8±28.5) min vs. (75.2±22.3) min, P=0.002], but the rate of intraoperative second extended resection for positive margin in OBCS group was significantly lower than that in TBCS group (3.2% vs.11.5%, P=0.027). The volume of resected specimen in OBCS group was significantly larger than that in TBCS group [(101.3±12.9) mL vs. (67.6±9.8) mL, P=0.013]. The excellent and good rate of breast cosmetic effect in OBCS group was significantly higher than that in TBCS group (86.3% vs. 37.4%, P=0.000). The subjective satisfaction rate in OBCS group was significantly higher than that in TBCS group (91.6% vs. 44.3%, P=0.000). There were no significant differences in intraoperative blood loss, axillary lymph node dissection, incidence of postoperative complications, total length of hospital stay, postoperative local recurrence rate, disease-free survival rate and overall survival rate between the two groups (all P>0.05).Conclusion The application of oncoplastic surgery in breast-conserving surgery for appropriate breast cancer patients can offer better cosmetic effect and better subjective satisfaction, improve the patients’ quality of life without increase of the risk of complications as well as tumor recurrence and metastasis. So, it is recommended to be used in clinical parctice.

4 Clinicopathologic analysis of 24 cases of myoid hamartoma of the breast

LIU Tao , ZHANG Zhaoxiang , YI Muhua , YANG Qiaorong

2022, 31(5):587-596. DOI: 10.7659/j.issn.1005-6947.2022.05.004

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Background and Aims Myoid hamartoma of the breast (MHB) is an extremely rare subtype of breast hamartomas, with only case reports documented in the literature. At present, its clinical and pathological features are not well understood, so it is easy to cause missed diagnosis and misdiagnosis. To raise awareness of this disease, herein, the authors report a case of MHB, combined with reviewing 23 cases of MHB reported in the literature, to investigate its histogenesis, clinicopathologic characteristics, and clinical diagnosis and treatment as well as the prognosis.Methods Retrospective clinicopathologic analysis was performed on one case of MHB treated in the authors’ hospital and 23 cases of MHB reported in China.Results All patients were female, and their age at onset ranged from 19 to 65 years, with an average age of (37±12.3) years. All the 24 patients had a solitary lesion, and the maximum diameter of the lesions ranged from 1.9 to 10.0 cm, with an average of (2.9±1.94) cm. The case reported by the authors had the largest tumor volume (10 cm in diameter) among the whole group, which accounted for 0.05% of the total 1 849 breast biopsy specimens and 0.1% of the total breast benign tumors in the authors’ hospital over the past 20 years. Imaging examinations showed that all tumors presented as a well-demarcated lump, but the images were nonspecific; ultrasound-guided core needle biopsy had certain diagnostic value. Naked-eye observation showed that all lesions were well-circumscribed, mobile and painless breast mass or nodule, and were similar to fibroadenoma. Twenty-one patients (87.5%) underwent simple breast lump excision, and 3 patients (12.5%) received extended breast mass excision. Fourteen patients (58.3%) had a clinical diagnosis record, but all were misdiagnosed or considered as breast fibroadenoma. The results of histopathological examination showed that all lesions were composed of randomly mixed mammary ducts, acini and fibroadipose tissue in varying proportions; distinctive well-differentiated smooth muscle tissue or myoid cells were seen in the tumors. Immunophenotypic analysis showed that there were diffuse and strongly positive staining for desmin, α-SMA, vimentin, MSA and h-caldesmon in the smooth muscle component in the tumors. Postoperative follow-up was obtained in 20 patients (83.3%) for an average of (18.6±15.4) months, reoccurrence occurred once in one case 10 months after operation, occurred twice in one case 36 and 41 months after operation, and occurred in none of the remaining cases.Conclusion MHB is a rare benign tumor with high misdiagnosis rate. Clinicians should enhance their understanding and diagnostic awareness of MHB. It should be differentiated from tumors such as breast fibroadenoma and other tumor-like lesions of the breast. MHB may recur, so extensive local resection should be adopted to ensure a negative margin, and regular postoperative follow-up should be performed.

5 Application of intelligent dose adjustment assistant system in postoperative endocrine suppression therapy for patients with papillary thyroid carcinoma

CHEN Chengkun , TAO Xuanbin , ZHANG Yingchao , DENG Xianzhao , GUO Bomin , DING Zheng , LI Ming , ZHOU Jian , BAO Yuqian , SHEN Li , ZHENG Yuanyi , FAN Youben

2022, 31(5):597-607. DOI: 10.7659/j.issn.1005-6947.2022.05.005

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Background and Aims The incidence of thyroid cancer is growing rapidly. Long-term endocrine suppression therapy after surgery for papillary thyroid carcinoma (PTC) is an important measure to reduce disease recurrence. However, multiple outpatient clinic visits of patients significantly increase the medical burden and costs, and different physicians may have different standards for drug dose adjustment. Therefore, an assistant medication dispensing system is needed to facilitate accurate dose adjustment in clinical settings. In this study, the authors independently developed and designed a specialized intelligent dose adjustment assistant system for postoperative endocrine suppression therapy, so as to facilitate and simplify the dose adjustment process in clinical practice.Methods According to the principle and related guidelines of thyroid stimulating hormone (TSH) suppression therapy, the medication adjustment goals and detailed rules of TSH suppression therapy were established, and were coded into computer language to build a dose adjustment software system combined with network server, and clients' and users' terminals. The patients who received TSH suppression therapy after surgery for PTC at the outpatient clinic from February 2021 to January 2022 were enrolled, and were categorized according to the postoperative time as initial treatment stage (<1 year) and follow-up stage (≥1 year). The general data were collected when the patients entered the study, which included gender, age, body mass index (BMI), scope of surgery and recurrence risk stratification, and the parameters were recorded during dose adjustment, which included the time of postoperative reexamination, the indexes of thyroid function, the number of cases with hyperthyroidism or hypothyroidism related symptoms, and the number of cases with good control (the TSH value was within the target range). The program of the intelligent dose adjustment assistant system included two computer-aided adjustments following the record of the results of the physician's adjustment. First of all, according to the parameters recorded when the patients entered the study, a new medication plan was automatically generated by the system, and the patients received levothyroxine treatment according to the new scheme until the second reexamination. In the second reexamination, the new parameters produced after dose adjustment were recorded, and a new medication scheme was generated again by the system, the patients were continuously treated with levothyroxine according to the second new scheme until the third reexamination, and the new parameters produced after medication adjustment were recorded at the end of the follow-up. The control rates of TSH level and other relevant clinical variables between the results of two system adjustments and the results of physician's adjustment before system adjustment were compared and analyzed.Results A total of 99 patients in initial treatment stage were included, 2 cases (2.0%) were lost to follow-up, and 97 cases completed dose adjustment follow-up. The control rates of TSH level of the two system adjustments were higher than that of the physician's adjustment (57.7% vs. 34.0%, P=0.001; 63.9% vs. 34.0%, P <0.001). There was no significant difference in the incidence of symptoms related to hyperthyroidism or hypothyroidism (P=0.791, P=0.267). A total of 50 patients in follow-up stage were included, and all of them completed dose adjustment follow-up. There was no significant difference in the control rate of TSH level between the first system adjustment and physician's adjustment (50.0% vs. 36.0%, P=0.143), but the control rate of TSH level of the second system adjustment was higher than that of physician's adjustment (66.0% vs. 36.0%, P=0.007). There was no significant difference in the incidence of symptoms related to hyperthyroidism or hypothyroidism (P=0.180, P=0.180). The results of subgroup analysis stratified by sex, BMI, scope of surgery and recurrence risk were generally consistent with the results of overall analysis. There were no statistical differences in control rates of TSH by physician's adjustment and two system adjustments between patients in initial treatment stage and follow-up stage (all P>0.05).Conclusion In the process of endocrine suppression therapy after surgery for PTC, compared with physician's adjustment, the intelligent dose adjustment assistant system has considerable safety and higher control rates of TSH level, and can better assist clinicians to accurately adjust levothyroxine dose in PTC patients after surgery. However, large sample-sized, multicenter and prospective studies are still needed to further verify the above conclusion.

6 Analysis of clinical characteristics and prognosis of thyroid cancer in children and adolescents

CHEN Yiru , LEI Yali , ZOU Lianhong , WU Yaqin , XIAO Xiangyuqin , ZHANG Chaojie

2022, 31(5):608-618. DOI: 10.7659/j.issn.1005-6947.2022.05.006

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Background and Aims Although the incidence rate of thyroid cancer among children and adolescents is considerably lower than that among adults, it is still increasing over time, and thyroid cancer has become one of the relatively common malignant tumors in children and adolescents. Compared with adults, thyroid cancer in children and adolescents have some different clinical characteristics, and further investigating these characteristics may facilitate more precise diagnosis and treatment planning. Therefore, this study was performed to investigate the clinicopathologic features and prognosis of thyroid cancer in children and adolescents through a retrospective analysis, so as to provide a reference for treatment decisions in clinical practice.Methods The data of 68 pediatric and adolescent patients (≤20 years old) undergoing surgery for thyroid diseases in the First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) from September 2014 to June 2021 were collected. The patients with thyroid cancer receiving follow-up were included for study. In addition, 22 adult patients with thyroid cancer were randomly selected as control. The differences in clinical characteristics and prognosis between the two groups of thyroid cancer patients were compared.Results Among the 68 pediatric and adolescent patients, 24 cases (35.29%) were pathologically diagnosed as thyroid cancer, of whom, 22 cases receiving a follow-up for 3 to 27 months. Of the 22 patients, 19 were females and 3 were males (6.33∶1); age ranged from 3 to 20 years with an average age of （16.73±4.52） years; the course of the disease ranged from 10 d to 5 years with an average of 9.5 months; hospital admission was mainly due to palpation of a painless mass in the neck; TI-RADS 4 and 5 nodules accounted for a high proportion (19/22, 86.36%) in preoperative thyroid ultrasound; 3 cases underwent thyroid lobectomy of the affected side, one case underwent thyroid lobectomy of the affected side plus contralateral subtotal thyroidectomy, 2 cases underwent thyroid lobectomy of the affected side plus contralateral proximal total thyroidectomy, and the remaining cases all underwent total thyroidectomy; 21 cases received central compartment lymph node dissection, 13 cases received lateral lymph node dissection, and one case did not undergo lymph node dissection. The postoperative pathology showed that 18 cases (81.82%) were papillary thyroid carcinoma (PTC), 3 cases (13.64%) were papillary thyroid microcarcinoma (PTMC), and one case (4.54%) was medullary thyroid carcinoma (MTC). After operation, unilateral recurrent laryngeal nerve injury occurred in 3 cases, laryngeal edema occurred in one case, hypoparathyroidism occurred in 2 cases, and chylous leakage occurred in one case after lymph node dissection in the left lateral cervical region. Recurrence occurred in one patient with MTC about 3 years later, and then the patient underwent extended bilateral lymph node dissection and targeted drug therapy. The gender distribution of thyroid cancer in children and adolescents was basically the same as that in adults; PTC was the most common pathological type of thyroid cancer for pediatric and adolescent thyroid cancer patients and adult thyroid cancer patients (95.45% vs. 100.00%), but the proportion of PTMC in the former was significantly lower than that in the latter (13.36% vs. 50.00%, P<0.05); in addition, the cervical lymph node metastasis accounted for 77.27% (17/22) in pediatric and adolescent patients, in which the proportion of bilateral cervical lymph node metastasis was significantly higher than that in adult patients (50.00% vs. 9.09%, P<0.05).Conclusion Thyroid cancer accounts for a relatively high proportion of thyroid diseases in children and adolescents. The patients' sex and pathological type of thyroid cancer in children and adolescents are similar to those in adults, but the tumor size at diagnosis is often larger than that of adults, and bilateral cervical lymph node metastasis is more likely to occur. However, after standardized treatment such as surgery, the overall prognosis is better.

7 Expression of long non-coding RNA FoxP4-AS1 in papillary thyroid carcinoma cells and its biological function

YANG Huifang , TANG Rui , LUO Xue , GAO Qingjun , CHEN Xinghong , ZHAO Daiwei

2022, 31(5):619-630. DOI: 10.7659/j.issn.1005-6947.2022.05.007

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Background and Aims The authors have previously found that the long non-coding RNA FoxP4-AS1 (lncRNA FoxP4-AS1) is abnormally expressed in papillary thyroid carcinoma (PTC) tissue, and its low expression is an independent risk factor for regional lymph node metastasis in PTC. However, its function and action mechanism remain unclear. Therefore, this study was conducted to investigate the expression of lncRNA FoxP4-AS1 in PTC cells, and make a preliminary analysis of its effect on the biological behavior of PTC cells.Methods The expressions of lncRNA FoxP4-AS1 in PTC cell lines (TPC-1, K1 cells) and normal thyroid follicular epithelial cells (Nthy-ori3-1 cells) were determined by qRT-PCR. In TPC-1 and K1 cells after transfection with FoxP4-AS1 overexpressing lentiviral vector or empty virus vector (negative control), the changes in biological functions were analyzed by CCK-8 assay, colony formation assay, EdU incorporation assay, Transwell assay and flow cytometry, respectively. The potential target genes of FoxP4-AS1 were predicted by GEPIA database and LncTar website, and then verified by Western blot analysis. Using above transfected cells, subcutaneous tumor models in mice were created, then, the growth of the xenograft tumors was observed and Ki-67 expressions in the tumors were determined by immunohistochemical staining. A preliminary analysis of the signaling pathways potentially associated with FoxP4-AS1 was performed by using the KEGG database.Results qRT-PCR results showed that the expression levels of lncRNA FoxP4-AS1 in the two types of PTC cells were significantly lower than that in the normal thyroid follicular epithelial cells (both P<0.05). Cell function experiments showed that the proliferation activity as well as invasion and migration abilities were significantly decreased with G₀/G₁ phase arrest in TPC-1 and K1 cells after transfection with FoxP4-AS1 overexpressing lentivirus vector compared with the negative control cells (all P<0.01). The GEPIA database and LncTar website predicted that there were potential interaction targets between FoxP4-AS1 and CDK4. Western blot results showed that the expression levels of CDK4/cyclinD1 in the two types of cells transfected with FoxP4-AS1 overexpressing lentivirus vector were significantly lower than those in their corresponding negative control cells (all P<0.05). In the subcutaneous tumor transplantation models, the PTC cells transfected with FoxP4-AS1 overexpressing lentivirus vector showed a slow growth in the mice, small volume of the formed tumor and low Ki-67 expression in the tumor compared with PTC cells transfected with empty virus vector. KEGG pathway enrichment analysis showed that the FoxP4-AS1 low expression was mainly enriched in PI3K-AKT-MTOR pathway, cell cycle, apoptosis, and immune regulation interactions, and the FoxP4-AS1 high expression was mainly enriched in DNA methylation and oxidative stress pathways.Conclusion The expression of lncRNA FoxP4-AS1 is down-regulated in PTC cells and is closely related to the malignant biological behavior of PTC cells. FoxP4-AS1 may exert its actions as a protective factor by suppressing the expression of CDK4/cyclinD1 and thereby inhibiting the proliferation of PTC cells.

8 Bioinformatics analysis of changes in genes associated with tumor-associated macrophages before and after neoadjuvant chemotherapy for breast cancer

CHEN Juan , JIANG Bin , HUANG Guo , HE Qiudong

2022, 31(5):631-639. DOI: 10.7659/j.issn.1005-6947.2022.05.008

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Background and Aims Breast cancer is the most prevalent malignancy in women worldwide, and chemotherapy is one of the most important treatment modalities for breast cancer. Recent studies have shown that chemotherapy may exert anti-tumor effects by enhancing anti-tumor immunity in the tumor microenvironment. Therefore, this study was conducted to identify the changes in tumor-associated macrophages (TAMs) and relevant genes before and after neoadjuvant chemotherapy (NAC) in breast cancer patients by bioinformatics analysis and to evaluate the effect of NAC on immune functions in breast cancer patients.Methods Information searching was performed by entering "Breast Cancer", "TAMs", "Chemotherapy" and selecting the human breast cancer tissue in the GEO database, and the GSE134600 dataset was selected for analysis. Differentially expressed genes (DEGs) in tissue samples from breast cancer patients before and after NAC were screened by R package (limma function). GO function enrichment and KEGG pathway analysis were performed for all DRGs. The protein interaction network of DEGs was visualized by Cytoscape software, and hub genes were screened and 10 hub genes were analyzed for mutations by cBioPortal. Immune cell distribution and correlation in GSE134600 data were evaluated using the R package “CIBERSORT”.Results A total of 751 DEGs (409 up-regulated and 342 down-regulated genes) were identified before and after NAC for breast cancer. The biology of DEGs was analyzed by GO enrichment for biological process（BP）, cellular component（CC）, and molecular function（MF）. In BP function, they were mainly enriched in type I interferon(IFN-I) signaling pathway/viral response and defense and viral life cycle; in CC function, they were mainly enriched in extrinsic components of cell membrane and cytoplasmic side of cell membrane; in MF function, they were mainly enriched in cytokine receptor binding, double-stranded RNA binding and lipopeptide binding. In the analysis of KEGG pathway enrichment, DEGs were mainly enriched in influenza A (H1N1), measles, hepatitis C, coronavirus disease COVID-19, NF-κB signaling pathway, EBV virus infection, NOD-like receptor signaling pathway, and amoeba disease signaling pathway. The top 10 hub genes with the highest degree of interaction with TAMs before and after NAC for breast cancer were screened by CytoHubba plug-in: IFIT1, ISG15, MX1, MX2, IRF7, RSAD2, IFIT3, IFI35, IFI6, and IFITM1. Multi-omics analysis revealed that IFIT1, MX1 and MX2 were mainly deletion mutations, IFIT1 mainly had deep gene deletion, while MX1 and MX2 were mainly associated with gene amplifications. The content of M0 macrophages, CD8⁺T cells and M2 macrophages in breast cancer tissues decreased after NAC, and M0 macrophages were positively correlated with memory B cells (r=0.64) and negatively correlated with unactivated CD4⁺ memory T cells (r=-0.66).Conclusion The identified DEGs associated with TAMs in breast cancer patients before and after NAC are closely related to interferon signaling pathway, suggesting that interferon signaling pathway may play an important role by altering TAMs in NAC. Meanwhile, M0 macrophages are significantly altered before and after NAC, indicating that chemotherapy may regulate the immune response to tumor by changing the distribution of M0 macrophages and immune function.

9 Bioinformatics analysis of expression of leucine-rich α 2 glycoprotein 1 in breast cancer and its function

ZHANG Yanshou , LIU Yunjiang

2022, 31(5):640-647. DOI: 10.7659/j.issn.1005-6947.2022.05.009

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Background and Aims Leucine-rich α 2 glycoprotein 1 (LRG1) is a member of the leucine-rich repeat (LRR) protein family. Recent studies have shown that LRG1 plays an important role in the occurrence, epithelial-mesenchymal transformation, invasion and metastasis, abnormal angiogenesis and prognosis of malignant tumors. However, the research on the expression, prognosis, function and potential mechanism of LRG1 in breast cancer remains to be elucidated. The purpose of this study was to systematically analyze the LRG1 expression in breast cancer and its significance based on bioinformatics approaches.Methods The expression of LRG1 in breast cancer and its relationship with clinicopathologic characteristics, prognostic value, interacting protein networks and functional enrichment were systematically analyzed by using the TCGA, Breast Cancer Gene-Expression Miner, UALCAN, Kaplan-Meier Plotter, GeneMANIA, DAVID and other databases.Results TCGA database analysis showed that the mRNA expression of LRG1 in breast invasive carcinoma was significantly higher than normal tissues (23.461 vs. 8.357, P<0.001). Among different molecular subtypes, LRG1 mRNA expression level in luminal subtype breast cancer was 37.462 (9.930-74.197), which was higher than that in HER-2 positive subtype and triple-negative subtype (both P<0.01); the LRG1 mRNA expression levels in stage I, II and III breast cancer were all higher than that in normal breast tissue (all P<0.05). Breast Cancer Gene-Expression Miner database analysis showed that the LRG1 mRNA expression levels in estrogen receptor (ER) and (or) progesterone receptor (PR) positive breast cancer were higher than those in ER and (or) PR negative breast cancer, and the LRG1 mRNA expression level in HER-2 negative breast cancer was higher than that in HER-2 positive breast cancer (all P<0.05); the LRG1 mRNA expression level in lymph node-positive breast cancer was higher than that in lymph node-negative breast cancer (P<0.000 1). Analysis of the TCGA survival data using the GEPIA online platform showed that both the overall survival (OS) and recurrence-free survival (RFS) rates in patients with high LRG1 expression were lower than those in patients with low LRG1 expression, but the differences did not reach a statistical significance (HR=0.81, P=0.200; HR=0.70, P=0.064); analysis of the TCGA survival data using Kaplan-Meier plotter revealed that LRG1 expression was not significantly correlated with the OS in luminal A, luminal B, and HER-2 positive subtypes (all P>0.05), but in the basal-like subtype breast cancer, the OS in patients with low LRG1 expression was better than that in patients with high LRG1 expression (HR=3.12, 95% CI=1.54-6.29, P<0.001). Using the GeneMANIA database for analysis, a total of 20 proteins interacting with LRG1 were screened. GO enrichment analysis showed that the LRG1 and the 20 its co-expression associated proteins were enriched in the extracellular regions, exosomes, blood particles, receptor complexes and other structures, and were involved in cell angiogenesis regulation, epithelial-mesenchymal transformation, hypoxia response and other relevant biological processes.Conclusion LRG1 expression is upregulated in breast invasive carcinoma and can predict the prognosis of some unfavorable subtypes of breast cancer. LRG1 may provide a new target for breast cancer treatment.

10 Expression of miR-18a-3p in liver cancer and the influence of its regulating ADCY1 expression on invasion and proliferation of liver cancer cells

PENG Emin , OUYANG Xiwu , WANG Wenlong , ZHENG Lu , YAO Lei , BAI Ning

2022, 31(5):648-657. DOI: 10.7659/j.issn.1005-6947.2022.05.010

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Background and Aims Studies have shown that a variety of microRNAs (miRNAs) may play crucial roles in the occurrence and development of liver cancer, and their action mechanisms still need to be studied and determined. Therefore, this study was conducted to further screen and validate the key miRNAs from the differentially-expressed miRNAs that have been reported in liver cancer, and then investigate their action mechanisms.Methods The common differentially-expressed miRNAs in liver cancer tissue and serum/plasm of liver cancer patients versus normal liver tissue and serum/plasm of healthy subjects were screened from the published studies. The expressions of goal miRNAs in normal liver cells and liver cancer cells were verified by qRT-PCR method. Using overexpression and inhibition strategies, the influences of goal miRNAs on invasion ability (Transwell invasion assay) and proliferation capacity (MTT assay) of liver cancer cells were observed, and also the expressions of goal miRNAs in 30 samples of clinical specimens were detected and their impacts on survival of liver cancer patients were analyzed through KM plotter website. The target genes of goal miRNAs were predicted and analyzed using miRDB and GEPIA databases and were further validated by reverse experiment and dual-luciferase reporter assay.Results There were 4 common up-regulated miRNAs (miR-18a-3p, miR-221-3p, miR-222-3p, miR-224-3p) and 2 down-regulated miRNAs (miR-26a-3p, miR-125b-3p) in liver cancer tissue (vs. normal liver tissue) and serum/plasma of liver cancer patients (vs. serum/plasma of healthy individuals). The qRT-PCR experiment confirmed that miR-18a was highly expressed and miR-26a was weakly expressed in liver cancer cells compared with normal liver cells (both P<0.05). Overexpression/inhibition of miR-18a expression promoted/reduced the invasion and proliferation capacities of liver cancer cells (all P<0.05), while overexpression/inhibition of miR-26a exerted confused influences on the invasion abilities and proliferation capacities of liver cancer cells. The results of analysis showed that ADCY1 was target gene of miR-18a-3p, overexpression of ADCY1 partially reversed the above actions of miR-18a-3p on liver cancer cells, and meanwhile, the up-regulated miR-18a-3p can inhibited the expression of ADCY1 by binding to the ADCY1 mRNA 3'UTR.Conclusion MiR-18a-3p may play a critical role in the occurrence and development of liver cancer. Its expression is up-regulated in liver cancer cells and tissues, which can promote the invasion and proliferation capacities of liver cancer cells by inhibiting the expression of downstream target gene ADCY1.

11 Research progress in analysis of sentinel lymph nodes after neoadjuvant chemotherapy for breast cancer

HUANG Ya , CHEN Jie

2022, 31(5):658-667. DOI: 10.7659/j.issn.1005-6947.2022.05.011

[Abstract](754) [HTML](913) [PDF 751.83 K](1256)

Abstract:
Axillary lymph node dissection (ALND) is frequently used in breast cancer surgery as the gold standard for assessing the status of axillary lymph nodes. However, with the development of medical techniques, more attention is paid to the patient's quality of life on the premise of ensuring survival and minimizing recurrence. The use of ALND in breast cancer patients is gradually declining due to its side effects such as arm lymphedema and shoulder dysfunction. Moreover, it is increasingly being replaced by sentinel lymph node biopsy (SLNB), which has the advantages of the less invasiveness and maintaining better patients' quality of life and is also a standard procedure to manage the axillary lymph nodes in early invasive breast cancer. Neoadjuvant chemotherapy (NAC), as an important part of systemic treatment of breast cancer, can not only shrink the tumor and increase the chance of radical surgery, but also increase the rate of breast conservation, and thereby bring benefits to more patients. However, the feasibility of performing SLNB after NAC is controversial, because the low detection rate and high false negative rate (FNR) of SLNB after NAC resulting from the influence of NAC exerted on the lymphatic vessels. It is an urgent clinical problem that how to help more breast cancer patients who meet eligibility criteria to avoid ALND to obtain more treatment benefits. Currently, many new technical approaches have been attempted to improve the detection rate and reduce the FNR of SLNB after NAC for breast cancer. Compared with using a single tracer, lymph node tracing in breast cancer using conventional dual tracer composed of radioisotope and blue dye, or combined with other new tracers such as carbon nanoparticle suspension, indocyanine green fluorescence, microbubble ultrasonography, superparamagnetic iron oxide, or using nanoparticle-assisted axillary staging, can significantly improve the detection rate of SLNB. Several large prospective trials have demonstrated that guarantee of removing ≥3 sentinel lymph nodes can dramatically reduce the FNR of SLNB; targeted ALND, a complement to SLNB, can facilitate a precise lymph node dissection by marking and locating the positive lymph nodes before operation, and its accuracy can be further enhanced by localization of radar reflectors, carbon tattoos, radioactive particles, magnetic particles, and intraoperative ultrasound. In addition, some recent studies have proposed to the combine with imaging examinations such as axillary ultrasound and CT lymphography, which can display the anatomical structure of lymph nodes and the surrounding lymphatic vessels clearly, to increase the certainty of clinicians, further improve the detection rate and reduce the FNR, but it has not been confirmed by data from large clinical trials yet. Herein, the authors systematically summarize the current research progress related to analysis of sentinel lymph nodes after NAC, aiming to provide some ideas and directions. The issue of how to make a choice in clinical practice to benefit more patients still needs a large number of studies to identify in the future.

12 Application of circulating free DNA in diagnosis and treatment of thyroid cancer

LI Ning , ZHU Chunyue , HONG Fangcheng , FENG Zheming , ZHENG Yuxin , ZHANG Fenghua

2022, 31(5):668-674. DOI: 10.7659/j.issn.1005-6947.2022.05.012

[Abstract](809) [HTML](695) [PDF 666.37 K](1361)

Abstract:
Thyroid cancer (TC) is the most common endocrine tumor. In recent years, with the population-based disease screening programs worldwide and the lifestyle changes, the incidence rate of thyroid cancer keeps rising. At present, the monitoring of diagnosis and treatment results of thyroid cancer mainly depends on invasive tissue biopsy or repeated imaging procedures with radiation exposure. Although the prognosis of most thyroid cancer patients is favorable, the recurrence and mortality rates are relatively high when extensive metastasis occurs. Therefore, developing a non-invasive, simple and repeatable detection technique in the early diagnosis and recurrence monitoring of thyroid cancer is particularly important. Liquid biopsy is a non-invasive testing procedure that can extract circulating tumor cells (CTC), circulating free DNA (cfDNA), microRNAs (miRNAs) and other biological samples from patients' blood, urine and other body fluids for analysis to obtain valuable biological information for tumor diagnosis and treatment, by which the clinicians can repeatedly and dynamically analyze the development of the patients'tumor, so as to achieve the purpose of accurate medical treatment. Among them, the cfDNA detection technique is the most important. It is a kind of acellular extracellular DNA existing in the body fluids of animals, plants and humans. Through the quantitative analysis, integrity detection, specific gene mutation and gene methylation analysis of cfDNA in blood, it plays a role in the early diagnosis, prediction of metastasis, recurrence and treatment effect monitoring of malignant tumors. Because of its non-invasive, high specificity and sensitivity, it has gradually become a hot spot in the research of cancer diagnosis and treatment, and its mechanism is still not fully understood so far. In recent years, the relevant literature evaluating the role of cfDNA detection in thyroid cancer has increased, which further shows that cfDNA detection technique can play an important role in the diagnosis, treatment and disease monitoring of thyroid cancer, and become a valuable tool to overcome the limitations of routine examination and monitoring methods of thyroid cancer. Therefore, cfDNA may become a new molecular marker to judge the effect of diagnosis and treatment of thyroid cancer. Here, the authors review the latest research progress of cfDNA in the diagnosis and treatment of thyroid cancer.

13 Research progress in the role of eosinophils in tumor immune microenvironment

WANG Siyu , WANG Kuansong

2022, 31(5):675-687. DOI: 10.7659/j.issn.1005-6947.2022.05.013

[Abstract](826) [HTML](612) [PDF 886.43 K](1720)

Abstract:
In recent years, the research on the occurrence and development process of malignant tumors and their treatment strategies has expanded to the integrated consideration of tumor tissue and tumor immune microenvironment (TIME). The TIME is composed of tumor cells, fibroblasts with their related matrix proteins, vascular endothelial cells, and immune cells, as well as a series of cytokines and chemokines, and extracellular matrix. The composition and phenotype of the TIME can affect tumor progression and response to treatment. A full understanding of each component of the TIME is helpful for the treatment decision-making and prognosis prediction. Eosinophils (EOS) are important components of TIME. They are produced from pluripotent stem cells in the bone marrow, and released into the blood as mature cells, and then migrate to tissues. This process is affected by the regulation of a variety of cytokines, chemokines and adhesion molecules, as well as by chemotaxis of a range of mediators secreted by EOS themselves, mast cells, fibroblasts and other components. Mature EOS possess primary and secondary granules that contain a range of cytotoxic basic proteins such as major basic protein (MBP), eosinophilic neurotoxin (EDN), eosinophilic cationic protein (ECP), and eosinophilic peroxidase (EPX), and can also secrete neurotrophic factors, interleukin, chemokines and other soluble components. At present, most studies on EOS focus on the analysis of the impact of EOS level on prognosis and the interaction between EOS and other components of the TIME. However, the signaling pathways and exact mechanisms associated with the pro-tumor or anti-tumor role of EOS are still unclear, and the relevant histological studies and clinical trials are also limited. So, this aspect needs to be investigated and improved further.

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Volume 31,Issue 5,2022 Table of Contents

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