CD101和Tim3在胃癌免疫微环境中的作用及其作为预后生物标志物的潜力。

The role of CD101 and Tim3 in the immune microenvironment of gastric cancer and their potential as prognostic biomarkers.

作者信息

Cheng Zhouyang, Lu Junfen, Chen Yaping, Cao Wei, Shao Qi

机构信息

Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.

Department of Chemotherapy, Afliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China.

出版信息

Int Immunopharmacol. 2025 Jan 27;146:113835. doi: 10.1016/j.intimp.2024.113835. Epub 2024 Dec 18.

DOI:10.1016/j.intimp.2024.113835

PMID:39700955

Abstract

BACKGROUND

Gastric cancer (GC) is a prevalent malignancy. Current treatment modalities, including surgery, chemotherapy, radiotherapy, and targeted therapy, have limitations in early detection and personalized treatment, necessitating the discovery of novel biomarkers and therapeutic strategies. This study aims to elucidate the molecular mechanisms underlying GC, focusing on the differentially expressed genes (DEGs) of CD101 Tim3 CD8 T cells (CCT precursors) and CD101 Tim3 CD8 T cells (CCT).

METHODS

Utilizing a multi-omics approach, including transcriptomic sequencing, single-cell RNA sequencing, cell communication analysis, and enrichment analysis.

RESULTS

We identified 140 genes significantly associated with overall survival in GC patients, including LYAR, ASCL2, and EMP2. A risk score model based on 14 prognostic genes was constructed, demonstrating a significant inverse correlation with survival time (p < 0.05). Immune response analysis indicated decreased infiltration of Activated B cells, CD56bright natural killer cells, and Monocytes in the high-risk group, while CD56dim natural killer cells and Gamma delta T cells were significantly increased, suggesting alterations in the immune microenvironment that influence patient prognosis. Furthermore, drug sensitivity analysis revealed potential responsiveness of high-risk patients to BI-2536, supporting personalized treatment approaches. Cell communication analysis indicated reduced intercellular interactions in PD-1 immunotherapy groups, highlighting the impact of immunotherapy on the tumor microenvironment. GSEA (Gene Set Enrichment Analysis) and GSVA (Gene Set Variation Analysis) revealed enrichment in DNA replication and proteasome pathways in high-risk groups, providing insights into the molecular mechanisms of GC.

CONCLUSIONS

This study established a foundation for future exploration of targeted therapies and personalized treatment strategies in GC.

摘要

背景

胃癌（GC）是一种常见的恶性肿瘤。目前的治疗方式，包括手术、化疗、放疗和靶向治疗，在早期检测和个性化治疗方面存在局限性，因此需要发现新的生物标志物和治疗策略。本研究旨在阐明GC的分子机制，重点关注CD101 Tim3 CD8 T细胞（CCT前体）和CD101 Tim3 CD8 T细胞（CCT）的差异表达基因（DEG）。

方法

采用多组学方法，包括转录组测序、单细胞RNA测序、细胞通讯分析和富集分析。

结果

我们鉴定出140个与GC患者总生存期显著相关的基因，包括LYAR、ASCL2和EMP2。构建了基于14个预后基因的风险评分模型，该模型与生存时间呈显著负相关（p < 0.05）。免疫反应分析表明，高风险组中活化B细胞、CD56bright自然杀伤细胞和单核细胞的浸润减少，而CD56dim自然杀伤细胞和γδT细胞显著增加，这表明免疫微环境的改变会影响患者预后。此外，药物敏感性分析显示高风险患者对BI-2536具有潜在反应性，支持个性化治疗方法。细胞通讯分析表明PD-1免疫治疗组中的细胞间相互作用减少，突出了免疫治疗对肿瘤微环境的影响。基因集富集分析（GSEA）和基因集变异分析（GSVA）显示高风险组中DNA复制和蛋白酶体途径富集，为GC的分子机制提供了见解。