Identification and validation of a CD4+ T cell-related prognostic model to predict immune responses in stage III-IV colorectal cancer

作者：Mengting Li, Weining Zhu, Yuanyuan Lu, Yu Raymond Shao, Fei Xu, Lan Liu, Qiu Zhao · 发表于：BMC Gastroenterology · 年份：2025 · DOI：10.1186/s12876-025-03716-2 · 被引用次数：8 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Immunotherapy and Immune Responses

CD4 + T cells play an indispensable role in anti-tumor immunity and shaping tumor development. We sought to explore the characteristics of CD4 + T cell marker genes and construct a CD4 + T cell-related prognostic signature for stage III-IV colorectal cancer (CRC) patients. We combined scRNA and bulk-RNA sequencing to analyze stage III-IV CRC patients and identified the CD4 + T cell marker genes. Unsupervised cluster analysis was performed to divide patients into two clusters. The LASSO and multivariate Cox regression were performed to establish a prognostic-related signature. RT-qpcr and immunofluorescence staining were performed to examine the expression of ANXA2 in CRC tissue. We found a higher infiltration abundance of activated memory CD4 + T cells was associated with improved prognosis in stage III-IV CRC patients. Patients were divided into two subgroups with distinct clinical and immunological behaviors based on CD4 + T cell marker genes. And then a prognostic signature consisting of six CD4 + T cell marker genes was established, which stratified patients into high- and low-risk groups. Immune spectrum showed that the low-risk group had higher immune cell infiltration than the high-risk group. Furthermore, the risk score of this signature could predict the susceptibility of stage III-IV CRC patients to immune checkpoint inhibitors and chemotherapy drugs. Finally, we validated that ANXA2 was enriched in Tregs and was associated with infiltration of Tregs in CRC tumor mi...