胃癌中失巢凋亡相关基因的鉴定：生物信息学及实验验证

Identification of Anoikis-Related Genes in Gastric Cancer: Bioinformatics and Experimental Validation.

作者信息

Song Chao, Liu Wenbo, Wang Xiaoyu, Liu Xin, Yang Zhiran, Wang Yingying, Zhao Qun, Li Yong, Zhang Mingming, Tan Bibo

机构信息

The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Department of Anesthesiology, Hebei General Hospital, Shijiazhuang, China.

出版信息

Cancer Med. 2025 Apr;14(8):e70907. doi: 10.1002/cam4.70907.

DOI:10.1002/cam4.70907

PMID:40263929

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12014852/

Abstract

INTRODUCTION

Distant metastasis is the main reason for the poor prognosis of gastric cancer, and anoikis refers to the cell death caused when cells detach from the extracellular matrix or adhere in incorrect locations, playing an important role in the distant metastasis of gastric cancer.

METHODS

Download the TCGA-STAD dataset and the anoikis gene set, and filter out the differentially expressed anoikis genes. Perform consensus clustering of gastric cancer samples, and conduct Weighted Gene Correlation Network Analysis (WGCNA), enrichment analysis, and immune infiltration analysis for the expression characteristics of each subtype, while also filtering the genes with differential expression between subtypes. Additionally, through COX survival analysis, identify anoikis genes related to gastric cancer prognosis and establish a nomogram. Finally, validate the differentially expressed gene CYP1B1 in vivo and in vitro through clinical samples, cell culture, and the establishment of an anoikis model.

RESULTS

Three subtypes of gastric cancer with anoikis genes were identified, each exhibiting different expression characteristics, biological pathways, and immune cell infiltration. The abundance of activated NK cells, memory B cells, and M2 macrophages showed significant differences among the three subtypes. We screened four differentially expressed gene sets and five genes (CYP1B1, EQTN, NRXN2, TBC1D3E, TCEAL5) among the three subtypes. Through survival analysis, we identified 33 independent prognostic genes and constructed a nomogram, with calibration curves indicating good consistency. Finally, we selected CYP1B1 for experimental validation, and in vivo and in vitro experiments demonstrated that CYP1B1 is highly expressed in gastric cancer, participates in the resistance to cell death in gastric cancer cells, and promotes the invasion, migration, and tumor progression of gastric cancer cells.

CONCLUSION

The expression patterns of subtypes based on differentially expressed genes related to anoikis in gastric cancer vary, providing theoretical support for the future of personalized treatment for gastric cancer.

摘要

引言

远处转移是胃癌预后不良的主要原因，失巢凋亡是指细胞从细胞外基质脱离或黏附于错误位置时引发的细胞死亡，在胃癌远处转移中起重要作用。

方法

下载TCGA-STAD数据集和失巢凋亡基因集，筛选出差异表达的失巢凋亡基因。对胃癌样本进行一致性聚类，并对各亚型的表达特征进行加权基因共表达网络分析（WGCNA）、富集分析和免疫浸润分析，同时筛选各亚型间差异表达的基因。此外，通过COX生存分析，鉴定与胃癌预后相关的失巢凋亡基因并建立列线图。最后，通过临床样本、细胞培养和建立失巢凋亡模型，在体内和体外验证差异表达基因CYP1B1。

结果

鉴定出具有失巢凋亡基因的三种胃癌亚型，各亚型表现出不同的表达特征、生物学通路和免疫细胞浸润。活化的自然杀伤细胞、记忆B细胞和M2巨噬细胞的丰度在三种亚型间存在显著差异。我们在三种亚型中筛选出四个差异表达基因集和五个基因（CYP1B1、EQTN、NRXN2、TBC1D3E、TCEAL5）。通过生存分析，我们鉴定出33个独立的预后基因并构建了列线图，校准曲线显示一致性良好。最后，我们选择CYP1B1进行实验验证，体内和体外实验表明CYP1B1在胃癌中高表达，参与胃癌细胞对细胞死亡的抵抗，并促进胃癌细胞的侵袭、迁移和肿瘤进展。