KRT15调节胃癌免疫微环境并抑制恶性表型

doi:10.16352/j.issn.1001-6325.2026.05.0658

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (5): 658-665.doi: 10.16352/j.issn.1001-6325.2026.05.0658

KRT15调节胃癌免疫微环境并抑制恶性表型

张帅¹, 王腾祺^2*, 田永静², 庞健², 孙海滨², 雷馨文²

1.内蒙古医科大学巴彦淖尔临床医学院,内蒙古呼和浩特 010110;
2.巴彦淖尔市医院胃肠外科,内蒙古巴彦淖尔 015000

收稿日期:2026-03-03 修回日期:2026-03-24 出版日期:2026-05-05 发布日期:2026-04-28
通讯作者: ^*wangtengqi@bynesyy.com
基金资助:
国家自然科学基金(82360117)

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

ZHANG Shuai¹, WANG Tengqi^2*, TIAN Yongjing², PANG Jian², SUN Haibin², LEI Xinwen²

1. Bayannur Clinical Medical College, Inner Mongolia Medical University, Hohhot 010110;
2. Department of Gastrointestinal Surgery, Bayannur Hospital, Bayannur 015000, China

Received:2026-03-03 Revised:2026-03-24 Online:2026-05-05 Published:2026-04-28
Contact: ^*wangtengqi@bynesyy.com

摘要/Abstract

摘要： 目的探讨角蛋白15(KRT15)在胃癌中的表达水平、功能及预后意义,并分析其在免疫微环境及恶性表型中的潜在机制。方法基于基因组图谱胃腺癌(TCGA-STAD)队列的转录组和临床数据,分析KRT15在胃癌组织中的表达水平及其预后价值;结合生物信息学分析评估KRT15的生物学意义;通过RT-qPCR和Western blot检测KRT15在胃癌组织和细胞系中的表达。构建稳定的KRT15敲低和过表达细胞模型,评估KRT15对胃癌细胞增殖、集落形成、迁移、侵袭、膜通透性及裸鼠移植瘤生长的影响,并检测PI3K/AKT信号通路活性的变化。结果 KRT15在胃癌组织中低表达(P＜0.05),且与总体生存较差相关。敲低KRT15可促进胃癌细胞的增殖、迁移、侵袭及成瘤能力,过表达KRT15则产生相反作用(P＜0.05)。生物信息学分析显示,KRT15相关基因主要富集于细胞增殖、黏附及PI3K/AKT相关通路,并与肿瘤免疫微环境的改变密切相关(P＜0.001);同时,KRT15表达降低伴随着PI3K和AKT磷酸化水平升高(P＜0.001)。结论 KRT15在胃癌中低表达,并与不良预后及肿瘤侵袭性表型相关。KRT15可能通过调控PI3K/AKT信号通路及胃癌免疫微环境抑制肿瘤恶性表型。

关键词: 角蛋白15(KRT15), 胃癌, PI3K/AKT通路, 肿瘤免疫微环境

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

中图分类号:

R735.2

张帅, 王腾祺, 田永静, 庞健, 孙海滨, 雷馨文. KRT15调节胃癌免疫微环境并抑制恶性表型[J]. 基础医学与临床, 2026, 46(5): 658-665.

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.

参考文献 11

[1]	甘宝平,刘屹.胃癌的肿瘤微环境与免疫治疗研究进展[J]. 临床医学进展,2025,15:1933-1945.
[2]	张卉, 甘世保, 李慧, 等. 沉默KRT17抑制人食管鳞癌细胞系KYSE-150增殖[J]. 基础医学与临床, 2025, 45: 1548-1556.
[3]	Zhang C, Liang Y, Ma MH, et al. KRT15, INHBA, MATN3, and AGT are aberrantly methylated and differentially expressed in gastric cancer and associated with prognosis[J]. Pathol Res Pract, 2019,215:893-899.
[4]	Xie Y, Zhou F, Li X, et al. KRT23 promotes prolifera-tion invasion and metastasis of gastric cancer through epithelial-mesenchymal transition mediated by the PI3K/AKT/mTOR signaling pathway[J]. Transl Cancer Res, 2025,14:6520-6535.
[5]	Morgos DT, Stefani C, Miricescu D, et al. Targeting PI3K/AKT/mTOR and MAPK signaling pathways in gastric cancer[J]. Int J Mol Sci, 2024,25:1848.doi: 10.3390/ijms25031848.
[6]	Wang J, Zhu G. Silencing of keratin 15 impairs viability and mobility while facilitating the doxorubicin chemosensitivity by inactivating the β-catenin pathway in liver cancer[J]. Oncol Lett, 2023,26:447.doi: 10.3892/ol.2023.14034.
[7]	Moon H, Zhu J, Donahue LR, et al. Krt5(+)/Krt15(+) foregut basal progenitors give rise to cyclooxygenase-2-dependent tumours in response to gastric acid stress[J]. Nat Commun, 2019,10:2225. doi: 10.1038/s41467-019-10194-0.
[8]	Zhang S, Liu H, Li X, et al. CCL20 secreted by KRT15high tumor cells promotes tertiary lymphoid structure formation and enhances anti-PD-1 therapy response in HPV+HNSCC[J]. Cell Death Dis, 2025,17:150.doi: 10.1038/s41419-025-08359-5.
[9]	Yang C, Zhong Z, Li C, et al. KRT15 drives immunosuppression in esophageal squamous cell carcinoma through GSK3β/β-catenin/CD276 signaling[J]. Exp Cell Res, 2026:114983. doi: 10.1016/j.yexcr.2026.114983.
[10]	Kohler KT, Goldhammer N, Demharter S, et al. Ductal keratin 15(+) luminal progenitors in normal breast exhibit a basal-like breast cancer transcriptomic signature[J]. NPJ Breast Cancer, 2022,8:81. doi: 10.1038/s41523-022-00444-8.
[11]	Rao X, Wang J, Song HM, et al. KRT15 overexpression predicts poor prognosis in colorectal cancer[J]. Neoplasma, 2020,67:410-414.

[1]	隆方文, 郑侠, 钱军, 章宜芬. 胃癌网膜转移机制的研究进展[J]. 基础医学与临床, 2026, 46(2): 282-287.
[2]	马悦, 黄从刚, 王远, 徐文青, 罗志华. 银杏叶提取物抑制人胶质瘤细胞系U87增殖和迁移[J]. 基础医学与临床, 2025, 45(9): 1144-1150.
[3]	贾纯亮, 梁磊, 李翰嵩, 王剑, 张磊, 李青科, 姚远. 灯盏花乙素抑制人胃癌细胞系MGC803增殖和迁移[J]. 基础医学与临床, 2025, 45(8): 1048-1053.
[4]	李文华, 王润霖, 康乾鹏, 黄梅, 郭正光, 张春林, 黄永胜. p97抑制剂EerⅠ诱导胃癌细胞系AGS的凋亡与铁死亡[J]. 基础医学与临床, 2025, 45(11): 1401-1408.
[5]	杜红蕾, 张锋, 郭海彦, 徐宁, 吴震. 大车前苷抑制人胃癌细胞系BGC823增殖和侵袭[J]. 基础医学与临床, 2025, 45(10): 1333-1340.
[6]	刘保清, 黄容, 卢艳, 李凯, 张宁, 刘长征, 宋伟. 胃癌类器官在基础研究与临床应用中的进展[J]. 基础医学与临床, 2024, 44(9): 1219-1222.
[7]	徐云聪, 郑金旭. CD27/CD70与特发性肺纤维化[J]. 基础医学与临床, 2024, 44(8): 1170-1174.
[8]	侯楠, 刘源, 高俊, 王晶, 袁萌. 全血NPM1、MCP-1和肠道菌群与胃癌进展及预后相关[J]. 基础医学与临床, 2024, 44(8): 1137-1142.
[9]	周玥, 童安莉. 嗜铬细胞瘤/副神经节瘤免疫微环境[J]. 基础医学与临床, 2024, 44(6): 742-747.
[10]	童玲, 张靖雯, 李帅, 段开鹏. 砷致胃癌的作用机制[J]. 基础医学与临床, 2024, 44(11): 1598-1602.
[11]	李炜康, 李东宝, 任嘉裕, 孙小童, 段开鹏, 周进. Ghrelin在胃癌中的作用[J]. 基础医学与临床, 2024, 44(10): 1460-1464.
[12]	郑彬彬, 林淑莹, 李德隆, 陈杰, 黄子成. 环状RNA ATP2B1靶向miR-452-5p降低胃癌细胞系的增殖和侵袭[J]. 基础医学与临床, 2023, 43(6): 882-888.
[13]	谢晓婷, 张雷, 张莉, 董凤, 刘颖, 李光华, 杨兴. ASH2L在幽门螺旋杆菌感染的人胃癌细胞系中的表达及临床意义[J]. 基础医学与临床, 2023, 43(3): 367-373.
[14]	杨蛟洋, 舒格格, 李东宝, 周进. 信号通路在胃癌转移中作用的研究进展[J]. 基础医学与临床, 2023, 43(11): 1707-1712.
[15]	刘东, 李庆妍, 王自全, 王丙武, 王保庆. 胃癌患者外周血miR-34a甲基化的检测及临床意义[J]. 基础医学与临床, 2023, 43(10): 1572-1576.

KRT15调节胃癌免疫微环境并抑制恶性表型

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

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 11

相关文章 15

编辑推荐

Metrics

本文评价