Multi-omic profiling identifies KRT1 as a predictor of immune infiltration and prognosis in gastroesophageal junction cancer

IF 3.9 4区生物学 Q1 GENETICS & HEREDITY

Functional & Integrative Genomics Pub Date : 2025-04-15 DOI:10.1007/s10142-025-01595-0

Tongkun Song, Jiangbo Chen, Pu Xing, Hao Hao, Xinying Yang, Bo Chen, Kai Xu, Jiadi Xing, Xiangqian Su

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引用次数: 0

Abstract

Gastroesophageal junction cancer (GEJ) is typically investigated alongside gastric or esophageal cancers. However, separate molecular profiles and immune cell infiltration of GEJ remain largely unknown. This study screened for hub genes in GEJ, studied their function and regulation in biological processes, and investigated their relationship with the infiltration of immune cells into tumors. Datasets were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus public databases. Molecular profiling revealed significant down-regulated expression of key genes in GEJ and enrichment in pathways related to epithelial cell differentiation and development, and structural constituents of skin epidermis. Prognostic analysis showed that patients with low KRT1, Desmocollin 2, and Envoplakin expression had a worse prognosis. There was a strong correlation between the levels of KRT1 and both the tumor mutational burden and immune cell infiltration. Single gene pathway enrichment analysis and in vitro experiments confirmed that cancer cell proliferation, migration, and invasion were suppressed by KRT1 via the AKT/mTOR pathway. In conclusion, this multi-dimensional study analyzed the molecular alterations and oncological mechanisms underlying the progression of GEJ. KRT1 is a promising candidate biomarker for the molecular and immunological characterization of GEJ and for prognosis prediction.

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多组学分析发现KRT1是胃食管结癌免疫浸润和预后的预测因子

胃食管结癌（GEJ）通常与胃癌或食管癌一起进行研究。然而，GEJ的单独分子特征和免疫细胞浸润在很大程度上仍然未知。本研究筛选GEJ中的枢纽基因，研究其在生物过程中的功能和调控，并探讨其与免疫细胞浸润肿瘤的关系。数据集从癌症基因组图谱和基因表达综合公共数据库下载。分子图谱显示GEJ关键基因表达显著下调，上皮细胞分化发育相关通路和皮肤表皮结构成分富集。预后分析显示，KRT1、Desmocollin 2和Envoplakin低表达的患者预后较差。KRT1水平与肿瘤突变负荷和免疫细胞浸润有很强的相关性。单基因通路富集分析和体外实验证实，KRT1通过AKT/mTOR通路抑制癌细胞的增殖、迁移和侵袭。总之，这项多维研究分析了GEJ进展的分子改变和肿瘤机制。KRT1是一种很有前途的候选生物标志物，用于GEJ的分子和免疫学表征以及预后预测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Functional & Integrative Genomics 生物-遗传学

CiteScore

3.50

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?