Volume 30,Issue 7,2021 Table of Contents

1 Concept innovations and challenges in surgical treatment of hepatocellular carcinoma

XIAO Liang , ZHOU Ledu

2021, 30(7):753-760. DOI: 10.7659/j.issn.1005-6947.2021.07.001

[Abstract](680) [HTML](1361) [PDF 891.59 K](1357)

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For hepatocellular carcinoma (HCC), surgery-oriented comprehensive treatment is the mainstream approach. Due to the insidious onset, only about one third of the newly diagnosed patients have a chance to receive a radical resection or liver transplantation. There are still controversies regarding the selection of laparoscopic or open surgery, and anatomic or nonanatomic liver resection in the academic community. In addition, the advent of targeted drugs represented by tyrosine kinase inhibitors and the immune checkpoint inhibitors represented by PD-1 antibodies leads the perioperative adjuvant therapy of HCC into a new era. A number of domestic medical centers have reported favorable results in preoperative conversion therapy for patients with initially unresectable advanced HCC, which offers new hope for improving the prognosis of these patients. Moreover, studies are also being actively carried out to evaluate the values of the preoperative neoadjuvant therapy for patients with initially resectable advanced HCC as well as the postoperative adjuvant therapy for HCC patients. Even more, scholars proposed the treatment strategies toward the achievement of no evidence of disease condition in HCC, according to the advances in adjuvant treatment modalities. In general, the therapeutic patterns for the treatment of HCC nowadays are already shifting toward those for the treatment of liver metastases from colorectal cancer. However, there are still a range of outstanding problems that urgently need to be validated by further clinical studies. This article focuses on the current situation of concept innovations and challenges in surgical treatment of HCC.

2 Meta-analysis of risk factors for pleural effusion after hepatectomy for liver cancer

LUO Lin , CHEN Hao , CHENG Yonglang , GAO Lin

2021, 30(7):761-771. DOI: 10.7659/j.issn.1005-6947.2021.07.002

[Abstract](589) [HTML](961) [PDF 1020.60 K](1249)

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Background and Aims The incidence of liver cancer is on the rise worldwide, which seriously affects human health. Hepatectomy is usually the first choice for the treatment of liver cancer, but its incidence of postoperative complications remains high and long-term efficacy needs to be improved. Pleural effusion is a common complication after hepatectomy. Studies have found that serum albumin level, alcohol consumption, right liver resection and other factors are closely related to the occurrence of pleural effusion after hepatectomy, but there is no unified conclusion at present. This study was conducted to investigate the risk factors for pleural effusion in patients with liver cancer after hepatectomy by means of Meta analysis, so as to provide a framework for reducing the incidence of pleural effusion after hepatectomy.Methods The studies concerning the influencing factors for pleural effusion in patients with liver cancer after hepatectomy published from the inception of databases to October 2020 were searched in several national and international databases. The literature was screened according to the inclusion and exclusion criteria, and the data extraction table was developed. Meta-analysis of each variable was performed using RevMan 5.3 software.Results A total of 13 case-control studies were included, involving 5 422 patients. Results of Meta-analysis showed that the main risk factors for pleural effusion after hepatectomy in patients with liver cancer included advanced age (MD=5.03, 95% CI=1.85-8.21), low serum albumin before surgery (OR=-1.28, 95% CI=-2.14-0.42), history of alcohol consumption (OR=1.46, 95% CI=1.03-2.06), concomitant chronic obstructive pulmonary disease (OR=3.15, 95% CI=1.15-8.59), hepatitis B virus and hepatitis C virus infection (OR=0.98, 95% CI=0.72-1.34; OR=2.17, 95% CI=1.18-4.00), ascites (MD=7.13, 95% CI=3.53-14.40), large tumor diameter (MD=1.30, 95% CI=0.27-2.33), prolonged hilar occlusion (MD=3.24, 95% CI=1.65-4.83), large intraoperative blood loss (MD=482.99, 95% CI=183.24-782.74), long operative time (MD=67.14, 95% CI=47.49-86.79), right liver tumor resection (MD=10.29, 95% CI=4.60-22.99), high postoperative total bilirubin (TBIL) level (MD=19.83, 95% CI=6.17-33.49), long prothrombin time after operation (MD=2.15, 95% CI=0.19-4.10), and low postoperative albumin (MD=-4.06, 95% CI=-7.07-1.06). The uncertain factors included preoperative TBIL, cirrhosis, and diabetes mellitus.Conclusion A total of 14 risk factors for pleural effusion after hepatectomy are identified in this study, and corresponding preventive measures against these risk factors are helpful for reducing the occurrence of pleural effusion after hepatectomy. The conclusion still needs to be verified by larger sample size and more rigorous multicenter randomized controlled trials in the future.

3 Analysis of risk factors for microvascular invasion in hepatocellular carcinoma and construction of preoperative predictive nomogram

DENG Jiazhong , JIA Weidong

2021, 30(7):772-779. DOI: 10.7659/j.issn.1005-6947.2021.07.003

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Background and Aims For patients with hepatocellular carcinoma (HCC), the effective prediction of presence or absence of microvascular invasion (MVI) is of great importance in clinical decision making, postoperative adjuvant therapy and systematic prognostic evaluation. Therefore, this study was conducted to investigate the risk factors for MVI in HCC and to establish a preoperative predictive nomogram, so as to provide a clinical reference.Methods The clinical data of 535 patients with HCC treated in Anhui Provincial Hospital from January 2017 to November 2020 were retrospectively analyzed. According to admission time, they were divided into model group (433 cases) and validation group (102 cases). Univariate and multivariate analyses were carried out to determine the independent risk factors for MVI. R software was used to establish a nomogram model to predict the preoperative MVI risk of hepatocellular carcinoma. Bootstrap analysis was used for internal validation of the model, and validation group was used for external validation of the model. C-index, calibration and receiver operating characteristic (ROC) curves were used to evaluate the predictive value of the nomogram.Results In the model group, multivariate analysis showed that NLR>2.282 (OR=1.864, 95% CI=1.184-2.933), GGT>60 IU/L (OR=2.554, 95% CI=1.631-4.001), lgAFP (OR=1.455, 95% CI=1.21-1.75), tumor size (OR=1.177, 95% CI=1.084-1.277) and absence of complete capsule (OR=2.019, 95% CI=1.286-3.171) were independent risk factors for preoperative prediction of MVI in patients with HCC. The C-index of the nomogram model established based no above factors were 0.785 (95% CI=0.742-0.828) and 0.824 (95% CI=0.737-0.91) in model group and validation group, respectively. The model fitted well with the calibration prediction curve. Based on the Youden index, the optimal critical value of the nomogram was 103. The sensitivity, specificity, positive predictive value and negative predictive value under the critical value were 86%, 61%, 67% and 82% in the model group, and 82%, 56%, 53% and 83% in the validation group, respectively.Conclusion NLR>2.282, GGT>60 IU/L, lgAFP, tumor size and absence of complete capsule were the independent risk factors for MVI in HCC. The established nomogram has a good preoperative performance in predicting MVI, which can directly analyze the preoperative risk of MVI and identify the high-risk population.

4 Short-term prognosis of left hemihepatectomy under laparoscopic ultrasound in treatment of primary liver cancer and its influence on liver function

HUA Xiaobin , LU Zhenglei , XIA Yunlian , LIU Xiaohu , XU Yongjian

2021, 30(7):780-788. DOI: 10.7659/j.issn.1005-6947.2021.07.004

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Background and Aims It is still a short period since the laparoscopic ultrasound (LUS) liver resection was employed in clinical practice, and the reports on the efficacy of its application in primary liver cancer (PLC) is also limited. Therefore, this study was conducted to investigate the short-term prognosis of LUS left hemihepatectomy for PLC and its influence on liver function.Methods The clinical data of 64 patients with PLC treated from January 2017 to January 2020 were retrospectively analyzed. Of the patients, 30 cases underwent left hemihepatectomy (LUS group) and 34 cases underwent conventional laparoscopic left hemihepatectomy (conventional group). The perioperative conditions and complications, and the serum albumin (ALB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), α-fetoprotein (AFP), thromboplastin time (APTT), fibrinogen (FIB), prothrombin time (PT) before surgery and 3 d and 1 month after surgery as well as the follow-up data were compared between the two groups of patients.Results There were no statistical differences in preoperative data and liver function parameters between the two groups of patients (all P>0.05). The average intraoperative blood loss of the LUS group was significantly lower than that of conventional group (322.64 mL vs. 395.94 mL, P<0.05). There were no statistical differences in terms of the operative time, distance from the cutting edge to the lesion, time for postoperative drainage tube retention, time to anal gas passage, and length of hospital stay between the two groups (all P>0.05). Middle hepatic vein injury occurred in none of the patients in LUS group, and occurred in 5 patients (14.71%) in conventional group, the difference was statistically significant (P<0.05). The incidence rates showed no statistical difference between LUS group and conventional group (13.33% vs. 23.53%, P>0.05). There were no statistical differences in APTT, FIB and PT as well as the ALB and AFP levels between the two groups on 3 d and 1 month after the surgery (all P>0.05); the ALT, AST and TBIL levels of LUS group were significantly lower than those of conventional group on 3 d after surgery (all P<0.05), which showed no significant differences on 1 month after surgery (all P>0.05). The median follow-up time was 13.5 (9-18) months. the recurrence and the mortality rates showed no statistical differences between LUS group and conventional group (10.00% vs. 17.65%, P=0.483; 3.33% vs. 5.88%, P=0.999).Conclusion The LUS left hemihepatectomy is safe and effective for the treatment of PLC, its short-term prognosis is similar to that of conventonal laparoscopic left hemihepatectomy. However, LUS is more effective for reducing intraoperative bleeding and protecting liver function in the early stage.

5 Diagnosis and surgical treatment of hepatic angiomyolipoma: a report of 19 cases

ZHAO Dexi , ZHANG Shaogeng , YU Lingxiang , DIAO Guanghao

2021, 30(7):789-797. DOI: 10.7659/j.issn.1005-6947.2021.07.005

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Background and Aims Hepatic angiomyolipoma (HAML) is a rare benign mesenchymal tumor of the liver, with no specific imaging features and low preoperative diagnosis rate. It is frequently misdiagnosed as hepatocellular carcinoma (HCC) or other hepatic benign tumors. This article reports the diagnosis and treatment process of 19 patients with HAML, so as to provide a reference and guidance for clinical practice.Methods The clinical data of 19 cases with HAML treated from January 2011 to December 2019 were retrospectively analyzed. Of the patients, 12 cases were females and 7 cases were males, with the age ranging from 28 to 61 years; lesion was found by health maintenance examination in 14 cases without clinical symptoms, 3 cases had abdominal pain, one case had intermittent abdominal distention, and one case had abdominal pain and diarrhea; one case was complicated with chronic hepatitis B and pulmonary abscess, one case was complicated with liver cirrhosis in compensatory period. All the 19 patients did not have angiomyolipoma of other organs such as kidney and lung, and none of them had tuberous sclerosis. The diameter of the tumors ranged from 1.3 to 12 cm, with an average diameter of (4.6±2.2) cm. The levels of AFP, CA19-9 and CEA were all within the normal range. Seven patients (36.8%) were diagnosed as HCC before operation, and 12 patients (63.2%) were considered as hepatic benign tumors that included 7 cases were diagnosed as hepatic adenoma, 2 cases were diagnosed as inflammatory pseudotumor, one case was diagnosed as hepatic cavernous hemangioma, one case was diagnosed as hepatic focal nodular hyperplasia, and one case was identified as HAML by preoperative ultrasound guided liver biopsy pathology.Results All patients underwent surgical treatment, including hepatic resection in 18 patients and ultrasound guided liver tumor biopsy and percutaneous puncture radiofrequency ablation of the liver tumor in one patient. The average operative time was (172.7±80.4) min, intraoperative blood loss was (456.6±528.1) mL, and length of hospital stay was (9.8±2.7) d. HAML was confirmed in all the 19 patients by pathological examination, in which seven cases were epithelioid angiomyolipoma. HMB-45 and SMA were positive in immunohistochemical staining. All patients recovered well after operation, and no complications such as liver failure, abdominal bleeding and bile leakage as well as death occurred. All patients were followed up, and no tumor recurrence and metastasis were found. All patients had good quality of life.Conclusions HAML belongs to benign tumor, and is difficult to diagnose before operation. Some patients were easily misdiagnosed as HCC. The final diagnosis depends on pathological and immunohistochemical analysis. Surgical resection is a safe and effective treatment option with good prognosis.

6 A comparative study of extra- versus intra-Glissonian approach in laparoscopic anatomical right posterior lobe resection

XIA Guoyi , LIU Sulai , SONG Yinghui , TAN Zhiguo , ZHENG He , PENG Chuang

2021, 30(7):798-804. DOI: 10.7659/j.issn.1005-6947.2021.07.006

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Background and Aims Extra-Glissonian approach was first proposed by Japanese scholar Takasaki and used in open surgery. With the enhancement of the concept of minimal invasiveness, surgery has gradually entered into the minimally invasive era, and hepatobiliary surgeons flexibly applied the extra-Glissonian approach in laparoscopic hepatectomy. This study was conducted to compare the safety and short-term efficacy of laparoscopic extra-Glissonian approach and intra-Glissonian approach in handling the hepatic pedicle of the right posterior lobe during anatomical right posterior lobotomy through a retrospective analysis.Methods The clinical data of 43 patients who underwent laparoscopic right posterior lobotomy in Hunan Provincial People's Hospital from January 2015 to September 2019 were retrospectively analyzed. Of the patients, the extra-Glissonian approach was used to deal with the hepatic pedicle of the right posterior lobe in 29 cases (extra-Glissonian group), and the intra-Glissonian approach was used to deal with the hepatic pedicle of the right posterior lobe in 14 cases (intra-Glissonian group). The operative time, intraoperative blood loss, length of hospital stay, postoperative complications, liver function indexes (total bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase) on the third day after surgery and prothrombin time were compared between the two groups.Results There were no statistical differences in preoperative data and disease constitution (hepatocellular carcinoma was dominant type in either group) between the two groups of patients (all P>0.05). The average operative time in extra-Glissonian group was significantly shorter than that in intra-Glissonian group (191.72 min vs. 231.54 min, P=0.001), while other variables that included the intraoperative blood loss, liver function indexes and prothrombin time on the postoperative day 3, length of hospital stay and incidence of complications shortly after surgery showed no statistical differences between the two groups of patients (all P>0.05). No perioperative death occurred in both groups.Conclusion Extra-Glissonian approach and intra-glissonian approach are equally safe in laparoscopic anatomical right posterior lobectomy. However, there should be sufficient preoperative imaging data and a full understanding of the anatomical structure and variation of the intrahepatic duct. Under the premise of mastery of surgical indications and skilled operation of laparoscopic surgery, the application of the extra-Glissonian approach can shorten the operative time and improve the operation efficiency.

7 Meta-analysis of liver resection assisted by three-dimensional reconstruction technique and two-dimensional imaging

QIAO Ting , WANG Junfeng , HU Pingping , JIN Yun , YANG Chao , SHI Wanhong

2021, 30(7):805-813. DOI: 10.7659/j.issn.1005-6947.2021.07.007

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Background and Aims The application of medical imaging three-dimensional reconstruction provides more intuitive and accurate data support for preoperative evaluation, surgical approach planning and surgical operation. However, there is limited support from high quality evidence for whether the three-dimensional reconstruction technique is more beneficial for liver resection. Therefore, this study was conducted to systematically evaluate the clinical effects of three-dimensional reconstruction and two-dimensional imaging in the assistance of hepatectomy.Methods The publicly published clinical studies comparing three-dimensional reconstruction and two-dimensional imaging for the assistance of hepatectomy were collected by searching several national and international online databases. Retrieval time was from the inception of the databases to December 2018. After data extraction and bias risk evaluation of the included studies, Meta-analysis was performed using RevMan5.3 software.Results A total of 12 clinical studies were included, involving 1 428 patients with 705 cases in two-dimensional group and 723 in three-dimensional group. Results of Meta-analysis showed that in three-dimensional group compared with two-dimensional group, the incidence of postoperative complications was decreased (OR=0.69, 95% CI=0.51-0.92, P=0.01), the intraoperative blood loss was reduced (MD=-63.85, 95% CI=-98.66-29.04, P=0.000 3), the incidence of postoperative liver failure was declined (OR=2.19, 95% CI=0.96-5.00, P=0.06), the postoperative recurrence rate was decreased (OR=0.29, 95% CI=0.16-0.53, P<0.000 1), and the postoperative survival rate was improved (OR=2.43, 95% CI=1.61-3.68, P<0.000 1).Conclusion The current data show that the use of three-dimensional reconstruction technology to assist liver resection can reduce the amount of intraoperative blood loss, reduce postoperative complications and recurrence rate, as well as improve postoperative survival rate. Therefore, the three-dimensional reconstruction technique is worthy of application and popularization in the assistance of hepatectomy.

8 Association of high mobility group box 1 with liver cancer cell repopulation and prognosis of liver cancer patients

HE Sijia , HUANG Qian , CHENG Jin

2021, 30(7):814-821. DOI: 10.7659/j.issn.1005-6947.2021.07.008

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Background and Aims Liver cancer is a common malignant tumor of the digestive system. Tumor recurrence is a major cause of treatment failure. High mobility group box 1 (HMGB1) has been found to be highly expressed in a variety of cancers, and play an important role in cancer development and progression. Therefore, this study was designed to investigate the relations of HMGB1 with the repopulation of liver cancer cells and the prognosis of liver cancer through in vitro repopulation model of liver cancer cells and database analysis.Methods Liver cancer Huh7 and Li7 cells were chosen for this study. The two types of cells were transfected with plasmids carrying firefly luciferin and green fluorescent protein (Fluc-GFP) gene to construct respective reporter cells Huh7-Fluc and Li7-Fluc cells. The Huh7 and Li7 cells treated with X-ray irradiation at a dose of 10 Gy were used as feeder cells and then co-cultured with their corresponding reporter cells to construct the in vitro repopulation models, using the systems of pure reporter cells and co-culture of the reporter cells and feeder cells without X-ray treatment as controls. The growth conditions of the reporter cells were evaluated by analyzing the changes in their luciferase activities via bioimaging, on which the effects of HMGB1 inhibitor glycyrrhizin (Gly) intervention were also observed. The HMGB1 expression levels of liver cancer tissue and tumor adjacent tissue as well as its association with the prognosis of liver cancer were analyzed using the TIMER2.0 and GEPIA2 tumor data analysis platforms.Results Compared with respective pure reporter cells group and reporter cells plus non-irradiated feeder cells co-culture group, the growth abilities of the reporter cells in both repopulation groups were significantly enhanced (all P<0.01). After Gly intervention, the growth abilities of the reporter cells in both repopulation models were significantly suppressed (both P<0.01), but the growth conditions of the pure reporter cells showed no significant changes (both P>0.05). The results of public database retrieval showed that the expression level of HMGB1 was higher in liver cancer than that in adjacent tissue (P<0.01), and the overall survival time of liver cancer patients with high HMGB1 expression level was significantly shorter than those with low HMGB1 expression level (P<0.01), and HMGB1 expression level was not correlated with disease free survival of liver cancer patients (P>0.05).Conclusion HMGB1 is involved in liver cancer cell repopulation induced by X-ray irradiation. The HMGB1 expression level in liver cancer tissue can be used as reference index for predicting the prognosis of overall survival of liver cancer patients, which may also provide a new strategy for the clinical treatment of liver cancer.

9 Construction of ceRNA network in liver ischemia/reperfusion injury and screening of the potential therapeutic agents

DENG Jiaqi , QIAN Baolin , ZHANG Liyun , KUANG Rong , LI Mingxing

2021, 30(7):822-835. DOI: 10.7659/j.issn.1005-6947.2021.07.009

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Background and Aims Liver ischemia/reperfusion (I/R) injury is a common pathophysiological change often involved in liver transplantation and hepatectomy. Competing endogenous RNA (ceRNA) regulatory network can participate in the occurrence and development of many diseases. However, there are only a few reports on the function of ceRNA network in liver I/R injury. This study was conducted to construct a ceRNA network related to liver I/R damage via bioinformatics approaches, and meanwhile to screen potential therapeutic drugs based on the differentially expressed genes.Methods The mRNA and miRNA expression chip data of liver I/R damage were obtained from the GEO database. Gene differential expression analysis was performed using the limma package in the R language, and the scatter plots, volcano plots and heat maps were drawn using the ggplot2 package. The protein-protein interaction (PPI) network was constructed using String database and Cytoscape software. The GO/KEGG function enrichment analyses were performed on the differentially expressed mRNAs screened out using Metascape database. The transcription factors that may regulate these differentially expressed genes were analyzed through the transcriptional regulatory network database. The miRNA-differentially expressed gene network was constructed using miRTarBase database. A ceRNA network was constructed through starBase: ceRNA database. The natural medicines that have potential effects on the expressions of key differentially expressed gene were screened using the Comparative Toxicogenomics Database (CTD).Results Two liver I/R injury mRNA data sets (GSE10654 and GSE117066) and one liver I/R injury miRNA data set (GSE72315) were obtained from the GEO database. A total of 16 genes up-regulated in I/R group and down-regulated in ischemic postconditioning (IPO) group, and 7 genes down-regulated in I/R group and up-regulated in IPO group were screened out by analyzing the mRNA expression data set using limma package and Venn diagram. The results of GO/KEGG functional enrichment analyses showed that the differential genes were mainly involved in the positive regulation of cell death and the biological process of response to extracellular stimuli, and participated in the MAPK signaling pathway. Transcription regulatory network database analysis revealed that six transcription factors (Trp53, Cebpb, Crebbp, Fos, Nfkb1 and SP1) may be involved in the regulation of these differentially expressed genes., two miRNA-mRNA axes (mmu-miR-32-5p-Btg2 and mmu-miR-9-5p-Mt2) may play an important role in liver I/R injury were obtained through miRTarBase database analysis and combined with the differential expression of miRNAs after I/R injury in the GSE72315 data set. Through starBase: ceRNA database analysis, 9 ceRNA networks were finally obtained, namely, the XIST/MEG8/LINC00963/MALAT1-miR-32-5p-Btg2 axis, XIST/NEAT1-miR-132-3p-Btg2 axis and HSPA9P1/RALGAPA1P1/RPS26P39-miR-9-5p-Dusp6 axis. Seven botanicals (quercetin, resveratrol, genistein, couestrol, curcumin, capsaicin, and scopolamine) that could exert potential therapeutic effects by reducing the expressions of key genes were screened out in the CTD database.Conclusion The important ceRNA networks in the process of hepatic I/R injury and potential therapeutic drugs are screened through bioinformatics analysis, which provide an important basis for further research of the pathogenesis of liver I/R injury and its therapeutic drugs.

10 Expressions of YTH family members in hepatocellular carcinoma and their prognostic values

HU Kuan , YAO Lei , LI Juanni

2021, 30(7):836-846. DOI: 10.7659/j.issn.1005-6947.2021.07.010

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Background and Aims All the YTH family members belong to the m6A reading protein, and are involved in the regulation of methylation in tumor development. However, the expression and specific role of the YTH family in hepatocellular carcinoma (HCC) remains to be further elucidated. Therefore, this study was conducted to explore the expression profiles and prognostic value of YTH family members and their relations with immune infiltration and relevant functions based on bioinformatics approaches.Methods The expression profiles of YTH family members in HCC and its subgroups were analyzed using UALCAN database, and their prognostic value in HCC were evaluated using Kaplan-Meier plotter. The co-expression profiles and genetic alterations of YTH family members were analyzed using the cBioPortal. The function and pathway enrichment analysis of YTH family were performed using WebGestalt database. The correlation analysis of YTH family and immune cell infiltration in HCC was conducted using TIMER 2.0 database.Results The mRNA expression levels of YTHDC1, YTHDC2, YTHDF1, YTHDF2 and YTHDF3 in HCC were significantly increased compared with those in normal liver tissues, and were closely related to clinical TNM stage and tumor grade, and their mRNA expression levels were progressively increased in 1, 2 and 3 stage/grade, while decreased in 4 stage/grade. Prognostic analysis showed that high expressions of both YTHDF1 and YTHDF2 were significantly associated with shorter overall survival (OS) and relapse-free survival (RFS). Analysis of the TCGA database and cBioPortal showed that the genetic alteration rate of YTHDF3 was 25%, which was the highest among YTH family members. GO function enrichment analysis showed that the main functions of YTH family were oriented toward metabolism and biosynthesis decomposition, especially hormone metabolism, sterol metabolism, lipid metabolism, drug catabolism, etc. The TIMER 2.0 database analysis showed that the expressions of most YTH family members were significantly positively correlated with the infiltration of CD4⁺ T cells, CD8⁺ T cells, B cells, neutrophils and dendritic cells, and negatively correlated with the infiltration of macrophages.Conclusion The molecular and expression profiles of YTH members were dysregulated in HCC. YTH family members (especially YTHDF1 and YTHDF2) are potential prognostic markers and new therapeutic targets. These findings may provide a new avenue for studying the mechanism and targeted therapy of HCC.

11 Latest developments in the treatment of advanced hepatocellular carcinoma

FENG Jianqi , WANG Zhiming

2021, 30(7):847-857. DOI: 10.7659/j.issn.1005-6947.2021.07.011

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Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive tract. Although the morbidity and mortality rates of HCC have been decreasing over the past 30 years in our country, China is still the country most afflicted by HCC worldwide. Despite the significant improvement in overall survival rate of HCC, the prognosis of patients with advanced HCC is still unsatisfactory and its treatment situation is very severe. In latest three years, a series of drugs and treatment strategies for advanced HCC have sprung up, which greatly improved the prognosis of the patients. Here, the authors summarize the progress in the treatment of advanced HCC in several fields with notable achievements.

12 Research progress in the relationship between all-trans retinoic acid and liver diseases and the associated molecular mechanisms

XU Zhaojun , CHEN Xiaobin , CAI Baojia , WANG Cheng , QIAO Wenjie , LIU Guangzhao , WANG Xinle , LIU Tao , MA Xiaoming

2021, 30(7):858-865. DOI: 10.7659/j.issn.1005-6947.2021.07.012

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All-trans retinoic acid (ATRA), also called retinoic acid and vitamin formic acid, is the main biologically active form of vitamin A. So far, the application of ATRA in the treatment of acute promyelocytic leukemia (APL) has exceeded 20 years, which is still the standard treatment for APL. With the continuous deepening of research, ATRA has been widely used in the treatment of thyroid cancer, lung cancer, gastric cancer, Kaposi’s sarcoma, ovarian cancer, bladder cancer, neuroblastoma, and other tumors, and is gradually extending to the differentiation therapy for more tumors. ATRA regulates gene expression by binding to nuclear retinoic acid receptor (RAR) or retinoid X receptor (RXR) and acting on the retinoic acid response element (RARE). It plays an important role in maintaining cell homeostasis, regulating cell cycle, signal transduction, transcription and translation, regulating the growth of tumor cells and promoting their apoptosis. The liver is the main place for vitamin A metabolism. Related studies have shown that ATRA is widely involved in the biological processes such as hepatitis, liver fibrosis and liver cancer cell proliferation, invasion and apoptosis by regulating the expressions of related proteins (including chemerin, signal protein Smad2/3, IGFBP-3, etc.). In addition, ATRA can promote the progression of non-alcoholic fatty liver disease by up-regulating the expression of chemerin. Hepatic stellate cells (HSC), also known as pericytes, are the main cell type involved in liver fibrosis. When the liver is damaged, HSC can be transformed into an activated state. The activated HSC secretes type I collagen (COL1α1) and α-smooth muscle actin (α-SMA) and thereby causes liver fibrosis, and vitamin A, the active form of ATRA, can reverse HSC activation and liver fibrosis. On the one hand, the Wnt signaling pathway participates in the formation of liver fibrosis by activating HSC, while ATRA can inhibit the occurrence of liver fibrosis by inducing RORα phosphorylation and inhibiting the signal transmission of Wnt/β-catenin; on the other hand, ATRA can inhibit the occurrence of liver fibrosis by inhibiting TGF-β1/Smad signal pathway expression, thereby exerting its anti-liver fibrosis effect. This article describes the mechanism by which ATRA inhibits the proliferation of liver cancer cells and induces apoptosis from multiple aspects that include the process by which ATRA inhibits the expression of Bcl-2 and Bcl-x proteins to induce cell apoptosis, or directly acts as inducing differentiation agent, the process of inducing apoptosis of liver cancer cells. In addition, ATRA can regulate the proliferation of liver cancer cells by regulating the expressions of related genetic materials, including inhibiting the proliferation of hepatocellular carcinoma by inhibiting insulin-like growth factors and promoting retinoic acid-induced gene 1 methylation. The application of ATRA in liver cancer has only been initially recognized in recent years. At present, there is no systematic understanding of the relationship between ATRA and liver diseases, and the specific regulatory mechanism in liver cancer needs to be further studied. A full understanding of the relationship between ATRA and liver diseases and the related molecular mechanisms involved can provide new strategies and directions for clinical diagnosis and treatment of liver diseases (non-alcoholic fatty liver disease, liver fibrosis, hepatocellular carcinoma and other diseases).

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Volume 30,Issue 7,2021 Table of Contents

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