基于炎症反应相关预后特征预测胃腺癌患者的免疫状态和基因突变

Predicting immune status and gene mutations in stomach adenocarcinoma patients based on inflammatory response-related prognostic features.

作者信息

Li Huanjun, Chen Jingtang, Chen Zhiliang, Liao Jingsheng

机构信息

Medical Oncology, Dongguan Institute of Clinical Cancer Research, Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan People's Hospital, Dongguan, 523888, China.

General Surgery Department, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan People's Hospital, Dongguan, 523888, China.

出版信息

Discov Oncol. 2025 Apr 9;16(1):497. doi: 10.1007/s12672-025-02210-1.

DOI:10.1007/s12672-025-02210-1

PMID:40205166

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11982005/

Abstract

BACKGROUND

Stomach adenocarcinoma (STAD) is an aggressive malignant tumor. Herein, we characterized the prognosis based on inflammatory response-related features and evaluated their potential impact on survival and immune status of STAD patients.

METHODS

Inflammation-related genes obtained from public databases were used to analyze the inflammatory response scores of STAD samples. The differentially expressed genes (DEGs) between STAD and adjacent gastric tissue were then analyzed using the "limma" package. Genes associated with STAD prognosis were obtained from the intersection of inflammation-related genes and DEGs. The key genes screened by last absolute shrinkage and selection operator (LASSO) Cox and stepwise regression analyses were used to construct prognostic models and nomograms. The tumor immune dysfunction exclusion (TIDE) algorithm was used to assess potential differences in immunotherapy response between high- and low-risk groups and to explore gene mutation signatures using the R software maftools package. In addition, GSEA was used to predict pathway characteristics between different subgroups. Finally, scratch and transwell assays were performed to explore the role of SERPINE1 in STAD cells.

RESULTS

We found that a high-inflammatory group was associated with poor prognosis in STAD patients. 14 inflammation-related DEGs out of 126 DEGs were identified to be associated with the prognosis of STAD patients, and the prognostic models and nomograms constructed from the subsequently identified key genes (SLC7A1, CD82, SERPINE1 ROS1 and SLC7A2) demonstrated a good predictive performance in terms of prognosis of STAD. Patients in the STAD high-risk group had higher StromalScore and TIDE scores. It was also found that patients in the STAD low-risk group may have a higher mutation burden. Enrichment analysis revealed significant enrichment of epithelial-mesenchymal transition, angiogenesis and KRAS pathways in the high-risk group. In-vitro experiments showed that down-regulation of SERPINE1 attenuated the migratory and invasive abilities of AGS cells.

CONCLUSION

This study provides new insights into prognostic prediction and immunotherapy for STAD from the perspective of the inflammatory response.

摘要

背景

胃腺癌（STAD）是一种侵袭性恶性肿瘤。在此，我们基于炎症反应相关特征对预后进行了表征，并评估了它们对STAD患者生存和免疫状态的潜在影响。

方法

从公共数据库中获取的炎症相关基因用于分析STAD样本的炎症反应评分。然后使用“limma”软件包分析STAD与相邻胃组织之间的差异表达基因（DEG）。从炎症相关基因和DEG的交集中获得与STAD预后相关的基因。通过最小绝对收缩和选择算子（LASSO）Cox分析和逐步回归分析筛选出的关键基因用于构建预后模型和列线图。使用肿瘤免疫功能障碍排除（TIDE）算法评估高风险组和低风险组之间免疫治疗反应的潜在差异，并使用R软件maftools软件包探索基因突变特征。此外，基因集富集分析（GSEA）用于预测不同亚组之间的通路特征。最后，进行划痕试验和Transwell试验以探讨丝氨酸蛋白酶抑制剂E1（SERPINE1）在STAD细胞中的作用。

结果

我们发现高炎症组与STAD患者的不良预后相关。在126个DEG中，有14个炎症相关DEG被确定与STAD患者的预后相关，随后确定的关键基因（溶质载体家族7成员1[SLC7A1]、CD82分子[CD82]、SERPINE1、ROS原癌基因1[ROS1]和溶质载体家族7成员2[SLC7A2]）构建的预后模型和列线图在STAD预后方面表现出良好的预测性能。STAD高风险组患者的基质评分和TIDE评分较高。还发现STAD低风险组患者可能具有更高的突变负担。富集分析显示高风险组中上皮-间质转化、血管生成和KRAS通路显著富集。体外实验表明，SERPINE1的下调减弱了AGS细胞的迁移和侵袭能力。