基于CD44相关差异基因构建胃癌预后模型及APOH的预后价值研究

Construction of a CD44-related prognostic model based on bioinformatics and the prognostic value of APOH in gastric cancer

摘要

目的：基于胃癌干细胞标志物CD44筛选相关差异基因（DEGs），构建胃癌预后模型，探讨APOH在胃癌预后中的作用。方法：从TCGA数据库下载胃癌RNA-seq转录组数据及生存资料。比较CD44在胃癌组织与癌旁组织中的表达差异，并作生存分析。根据CD44的差异表达获得DEGs，行GO及KEGG富集分析。构建蛋白与蛋白交互作用（PPI）网络，筛选关键节点基因。LASSO-Cox回归筛选预后相关基因并构建预后模型，绘制ROC、DCA、校准曲线并计算C-index评估模型预测效能。对PPI与LASSO-Cox回归结果的交集基因APOH行表达及生存分析，利用CIBERSORT算法对APOH行肿瘤免疫浸润细胞分析。结果：CD44在胃癌样本中高表达，且预示预后不良。富集分析显示693个DEGs主要参与细胞外基质重塑、细胞骨架调控及体液免疫相关通路。LASSO-Cox回归共筛选出20个预后相关基因。基于这些DEGs构建预后模型，结果显示，该模型对胃癌患者1、3和5年生存率具有较好的预测能力。免疫浸润分析显示，APOH表达与B细胞相关亚群及M2型巨噬细胞的浸润程度显著相关。结论：基于CD44相关DEGs构建的预后模型对胃癌患者具有一定的预测价值。APOH可能通过调控体液免疫反应及免疫抑制性细胞浸润参与胃癌进展，有望成为评估胃癌预后及免疫治疗的靶点。

Abstract

Objective: To screen differentially expressed genes(DEGs) associated with the gastric cancer stem cell marker CD44, construct a prognostic model for gastric cancer, and investigate the prognostic value of APOH in gastric cancer. Methods: RNA-seq transcriptome data and corresponding survival information of gastric cancer were downloaded from The Cancer Genome Atlas(TCGA) database. The different expression of CD44 gastric cancer tissues and normal tissues were analyzed, and its association with patient survival was evaluated. Gastric cancer samples were divided into high- and low-expression groups according to the median CD44 expression level, followed by differential expression analysis to identify differentially expressed genes(DEGs). GO and KEGG enrichment analyses were performed. The protein-protein interaction(PPI) network of DEGs was constructed using the STRING database and Cytoscape software to identify key node genes. Prognosis-related genes were further screened using LASSO-Cox regression analysis, and a prognostic model was established. Plot ROC curves, DCA curves, and calibration curves, and calculate the C-index to evaluate the predictive performance of the model. Subsequently, perform multivariate Cox analysis combining the risk score with age, gender, and TNM stage. The intersecting gene APOH between the PPI analysis and LASSO-Cox regression results was subjected to expression and survival analyses. In addition, the correlation between APOH expression and tumor-infiltrating immune cells was analyzed using the CIBERSORT algorithm. Results: CD44 was significantly upregulated in gastric cancer tissues, and its high expression was closely associated with poor prognosis. A total of 693 DEGs were identified based on CD44 expression grouping. Enrichment analyses indicated that these DEGs were mainly involved in extracellular matrix remodeling, cytoskeletal regulation, and humoral immune-related pathways. LASSO-Cox regression analysis identified 20 prognosis-related genes and established a prognostic model with good predictive performance for 1-, 3-, and 5-year survival. Multivariate Cox analysis showed that the risk score was an independent prognostic factor for survival. APOH was identified as a key gene by intersecting the results of PPI analysis and LASSO-Cox regression. Although the different expression of APOH between gastric cancer tissues and adjacent normal tissues was not statistically significant, high APOH expression was significantly associated with poorer survival outcomes. Immune infiltration analysis clued that APOH expression was significantly correlated with the infiltration levels of B cell-related subsets and M2 macrophages. Conclusion: The prognostic model constructed based on CD44-related differentially expressed genes shows potential predictive value for gastric cancer prognosis. APOH may be involved in gastric cancer progression by regulating humoral immune responses and the infiltration of immunosuppressive cells, providing new insights for prognostic evaluation and the exploration of immunotherapeutic targets in gastric cancer.

关键词

胃癌 / CD44 / APOH / 生物信息学 / 预后模型

Key words

Gastric cancer / CD44 / APOH / Bioinformatics / Prognostic model

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基金资助

国家自然科学基金(32360162)

陕西省教育厅专项科研计划项目(23JK0732)