KRT15调节胃癌免疫微环境并抑制恶性表型OA

Objective To investigate the expression pattern,function,potential clinical use of prognosis and reg-ulatory 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 ex-pression 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 exam-ined.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 tumori-genic 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 prolif-eration,adhesion,and PI3K/AKT signaling and were closely associated with alterations in the tumor immune mi-croenvironment(P＜0.001).In addition,reduced KRT15 expression was accompanied by increased phosphoryla-tion 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.