胆囊鳞状细胞癌预后模型的构建与验证
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1.四川省绵阳市中医医院 普通外科,四川 绵阳 621000;2.成都中医药大学医学技术学院,四川 成都 611137;3.四川省绵阳市中心医院 血管外科,四川 绵阳 621000

作者简介:

黄坤,四川省绵阳市中医医院主治医师,主要从事普外科基础与临床方面的研究。

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Construction and validation of the prognosis model for gallbladder squamous cell carcinoma
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1.Department of General Surgery, Mian Yang Traditional Chinese Medicine Hospital, Mianyang, Sichuan 621000, China;2.College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China;3.Department of General Surgery, Division of Vascular Surgery, Mian Yang Central Hospital, Mianyang, Sichuan 621000, China

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    摘要:

    背景与目的 胆囊鳞状细胞癌(GSCC)是胆囊癌中一种罕见的病理学类型,占胆囊癌的1%~4%。该类型肿瘤预后差,目前关于GSCC的文献报道主要是个案报道和小样本系列病例报道,由于缺乏大样本高质量的临床研究证据,目前临床上尚无针对GSCC的治疗指南、共识和个体化的预后评价工具。因此,本研究通过SEER数据库中的大样本数据构建GSCC患者预后列线图,旨在精准化、个体化评价GSCC患者的预后,为临床决策制定提供参考。方法 提取SEER 数据库中2000—2019年期间经病理确诊的GSCC患者的临床资料,按照7∶3的比例,将数据随机划分为训练集和验证集,在训练集中,分别采用多变量Cox比例风险模型和LASSO回归筛选影响GSCC患者预后的独立因素,利用这些因素,构建用于预测GSCC患者在3个月和6个月的肿瘤特异性生存期(CSS)和总生存期(OS)的列线图模型。随后,在训练集中,利用一致性指数(C指数)、ROC曲线和校准曲线,分别在训练集和验证集,对模型进行内部和外部验证,以评估模型的准确度和预测能力。结果 本研究共纳入257例患者,其中训练集179例,验证集78例。在训练集和验证集中,患者的中位随访时间分别为3(1~7)个月和4(2~8)个月。两组之间基线资料均衡可比。多变量Cox比例风险模型分析显示,年龄、SEER分期、手术和化疗是GSCC患者OS和CSS的独立影响因素(均P<0.05)。LASSO回归分析显示,年龄、SEER分期、放疗、手术和化疗与GSCC患者的OS相关;年龄、SEER分期、手术和化疗与GSCC患者的CSS相关。基于这些独立预后影响因素,构建了用于预测GSCC患者在3、6个月的OS和CSS的列线图。对模型的验证结果表明,训练集和验证集中,OS的C指数分别为0.739(95% CI=0.700~0.780)和0.729(95% CI=0.660~0.800);CSS的C指数分别为0.750(95% CI=0.710~0.790)和0.741(95% CI=0.670~0.810)。ROC曲线分析显示,曲线在训练集和验证集的AUC值均>0.8;校准曲线分析表明,通过模型预测的3、6个月的OS和CSS与GSCC患者真实的3、6个月的OS和CSS有较好的重合,两者均靠近理想的45°参考线,表现出良好的一致性。结论 年龄、SEER分期、手术、放疗和化疗是GSCC患者预后的独立影响因素。所构建的列线图预测模型具有良好的预测价值,有利于临床对GSCC患者选择个性化治疗。

    Abstract:

    Background and Aims Gallbladder squamous cell carcinoma (GSCC) is a rare histopathological subtype of gallbladder cancer, accounting for 1% to 4% of cases. This tumor type is associated with poor prognosis. Currently, the literature on GSCC mainly consists of case reports and small-sample case series. Due to the lack of large-sample high-quality clinical research evidence, there are no established treatment guidelines, consensus, or personalized prognostic assessment tools for GSCC. Therefore, this study aimed to construct prognostic nomograms for GSCC patients using large-scale real-world data from the SEER database to provide precise and individualized prognosis assessment for GSCC patients, offering valuable references for clinical decision-making.Methods Clinical data of GSCC patients pathologically diagnosed between 2000 and 2019 were extracted from the SEER database. The data were randomly divided into training and validation sets in a 7∶3 ratio. In the training set, a multivariate Cox proportional hazards model and LASSO regression were used to identify independent prognostic factors for the survival of GSCC patients. These factors constructed nomogram models to predict tumor-specific survival (CSS) and overall survival (OS) at 3 and 6 months for GSCC patients. Subsequently, the models were internally and externally validated in training and validation sets using the concordance index (C-index), ROC, and calibration curves to assess their accuracy and predictive capacity.Results A total of 257 patients were included in this study, 179 in the training and 78 in the validation set. The median follow-up times were 3 (1-7) months in the training set and 4 (2-8) months in the validation set. Baseline characteristics were comparable between the two groups. The multivariate Cox proportional hazards model analysis revealed that age, SEER stage, surgery, and chemotherapy were independent factors for OS and CSS in GSCC patients (all P<0.05). LASSO regression analysis indicated that age, SEER stage, radiotherapy, surgery, and chemotherapy were associated with OS; age, SEER stage, surgery, and chemotherapy were correlated with CSS in GSCC patients. Nomograms for predicting OS and CSS at 3 and 6 months were developed based on these independent prognostic factors. Validation results demonstrated C-index values of 0.739 (95% CI=0.700-0.780) and 0.729 (95% CI=0.660-0.800) for OS in the training and validation sets, respectively; C-index values of 0.750 (95% CI=0.710-0.790) and 0.741 (95% CI=0.670-0.810) for CSS in the same sets. ROC curve analysis indicated AUC values >0.8 in both training and validation sets. Calibration curve analysis showed good agreement between predicted and actual OS and CSS at 3 and 6 months for GSCC patients. Both were closely situated near the ideal 45° reference line, demonstrating high consistency.Conclusion Age, SEER stage, surgery, radiotherapy, and chemotherapy are independent prognostic factors for GSCC patients. The constructed nomogram prediction models exhibit favorable predictive value and facilitate personalized treatment selection for GSCC patients in the clinical setting.

    表 1 GSCC患者的临床基线特征[n(%)]Table 1 The baseline demographics and clinical characteristics of patients with GSCC [n (%)]
    表 3 训练集和验证集中模型的C指数和AUC值Table 3 C-index and AUC values of the model in the training and validation sets
    图1 基于多变量Cox回归分析森林图 A:OS;B:CSSFig.1 Forest plots using multivariate Cox regression analysis A: OS; B: CSS
    图2 基于LASSO回归的特征选择 A:LASSO回归系数随Log(λ)的变化曲线(OS);B:基于10折交叉验证C指数随Log(λ)的变化曲线(OS);C:LASSO回归系数随Log(λ)的变化曲线(CSS);D:基于10折交叉验证C指数随Log(λ)的变化曲线(CSS)Fig.2 Feature selection based on LASSO regression A: Curve of LASSO regression coefficients with changing Log(λ) (OS); B: Curve of 10-fold cross-validated C-index with changing Log(λ) (OS); C: Curve of LASSO regression coefficients with changing Log(λ) (CSS); D: Curve of 10-fold cross-validated C-index with changing Log(λ) (CSS)
    图3 训练集中GSCC患者基于5个变量的OS曲线Fig.3 OS curves for GSCC patients in the training set based on five variables
    图4 训练集中GSCC患者基于5个变量的CSS曲线Fig.4 CSS curves for GSCC patients in the training set based on five variables
    图5 预测GSCC患者3、6个月预后的列线图 A:OS;B:CSSFig.5 Nomograms predicting the 3- and 6-month prognosis for GSCC patients A: OS; B: CSS
    图6 训练集和验证集中模型3、6个月预测能力验证的ROC曲线Fig.6 ROC curves for the 3- and 6-month predictive ability validation of the model in the training and validation sets
    图7 训练集和验证中3、6个月OS与CSS的校准曲线Fig.7 Calibration curves for 3- and 6-month OS and CSS in the training and validation sets
    图8 不同风险患者的生存曲线 A:训练集OS;B:训练集CSS;C:验证集OS;D:验证集CSSFig.8 Survival curves for OS and CSS of patients with different risks A: OS for the training set; B: CSS for the training set; C: OS for the validation set; D: CSS for the validation set
    表 2 GSCC患者OS与CSS影响因素的单变量Cox分析Table 2 Univariate Cox regression analysis for CSS and OS in GSCC patients
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黄坤,黄正红,赵攀,赵平武,何运胜,白斗.胆囊鳞状细胞癌预后模型的构建与验证[J].中国普通外科杂志,2023,32(8):1187-1198.
DOI:10.7659/j. issn.1005-6947.2023.08.007

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  • 收稿日期:2023-04-19
  • 最后修改日期:2023-07-21
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  • 在线发布日期: 2023-11-03