Liu Xiaolong, Ma Bin, Chen Mali, Zhang Yaqing, Ma Zhen, Chen Hao
NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China.
Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China.
Front Genet. 2021 Oct 25;12:720849. doi: 10.3389/fgene.2021.720849. eCollection 2021.
Chemotherapy resistance based on fluorouracil and cisplatin is one of the most encountered postoperative clinical problems in patients diagnosed with gastric cancer (GC), resulting in poor prognosis. This study aimed to combine autophagy-related genes (ARGs) to investigate the susceptibility patients with GC to postoperative chemotherapy. Based on The Cancer Genome Atlas (TCGA) database, gene expression data for GC patients undergoing chemotherapy were integrated and analyzed. Prognostic genes were screened based on univariate and multivariate analysis regression analysis. Subjects were divided into high-risk and low-risk groups according to the median risk score. Kaplan-Meier method was used to evaluate OS and DFS. The accuracy of the prediction was determined by the subject operating characteristic curve analysis. In addition, stratified analyses based on different clinical variables was performed to assess the correlation between risk scores and clinical variables. Quantitative real-time (qRT) PCR was used to verify the expression of CXCR4 in GC tissues and cell lines. A total of nine ARGs related to the prognosis of chemotherapy patients were screened out. Compared with normal gastric mucosa cell, CXCR4 showed elevated expression in GC and was significantly associated with survival. Based on GEO and TCGA databases, the model accurately predicted DFS and OS after chemotherapy. This study established prognostic markers based on nine genes, predicting that ARGs are related to chemotherapy susceptibility of GC patients, which can provide better individualized treatment regimens for clinical practice.
基于氟尿嘧啶和顺铂的化疗耐药是胃癌(GC)患者术后最常见的临床问题之一,导致预后不良。本研究旨在结合自噬相关基因(ARGs)来研究GC患者对术后化疗的易感性。基于癌症基因组图谱(TCGA)数据库,对接受化疗的GC患者的基因表达数据进行整合和分析。通过单因素和多因素回归分析筛选预后基因。根据中位风险评分将受试者分为高风险组和低风险组。采用Kaplan-Meier法评估总生存期(OS)和无病生存期(DFS)。通过受试者工作特征曲线分析确定预测的准确性。此外,基于不同临床变量进行分层分析,以评估风险评分与临床变量之间的相关性。采用定量实时(qRT)PCR验证CXCR4在GC组织和细胞系中的表达。共筛选出9个与化疗患者预后相关的ARGs。与正常胃黏膜细胞相比,CXCR4在GC中表达升高,且与生存显著相关。基于GEO和TCGA数据库,该模型准确预测了化疗后的DFS和OS。本研究基于9个基因建立了预后标志物,预测ARGs与GC患者的化疗易感性相关,可为临床实践提供更好的个体化治疗方案。