KRT15 regulates the immune microenvironment and suppresses malignant phenotypes in gastric cancer

doi:10.16352/j.issn.1001-6325.2026.05.0658

Abstract

Abstract: Objective To investigate the expression pattern, function, potential clinical use of prognosis and regulatory mechanisms of keratin 15 (KRT15) in gastric cancer. Methods Transcriptomic and clinical data from the The Cancer Genome Atlas Stomach Adenocarcinoma(TCGA-STAD)cohort were analyzed to evaluate the expression level and prognostic value of KRT15 in gastric cancer. Bio-informatic analyse was performed to assess the biological significance of KRT15. KRT15 expression in gastric cancer tissues and cell lines was examined by RT-qPCR and Western blot. Stable KRT15-knockdown and KRT15-over-expression cell models were established to evaluate the effects of KRT15 on gastric cancer cell proliferation, colony formation, migration, invasion,membrane permeability and xenograft tumor growth in nude mice. Changes in PI3K/AKT signaling activity were also examined. Results KRT15 was down-regulated in gastric cancer tissues (P＜0.05) and low KRT15 expression was associated with poor prognosis. KRT15 knockdown promoted the proliferation, migration, invasion, and tumorigenic capacity of gastric cancer cells, whereas KRT15 over-expression exerted the opposite effects (P＜0.05). Bio-informatics analyses showed that KRT15-related genes were mainly enriched in pathways related to cell proliferation, adhesion, and PI3K/AKT signaling and were closely associated with alterations in the tumor immune microenvironment(P＜0.001). In addition, reduced KRT15 expression was accompanied by increased phosphorylation of PI3K and AKT (P＜0.001). Conclusions KRT15 is down-regulated in gastric cancer, which is associated with poor prognosis and aggressive tumor phenotypes. KRT15 may suppress malignant phenotypes of gastric cancer by regulating the PI3K/AKT signaling pathway and the tumor immune microenvironment.

Key words: keratin 15(KRT15), gastric cancer, PI3K/AKT pathway, tumor immune microenvironment

CLC Number:

R735.2

ZHANG Shuai, WANG Tengqi, TIAN Yongjing, PANG Jian, SUN Haibin, LEI Xinwen. KRT15 regulates the immune microenvironment and suppresses malignant phenotypes in gastric cancer[J]. Basic & Clinical Medicine, 2026, 46(5): 658-665.

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