角蛋白18在卵巢癌中的表达特征及其与患者生存和肿瘤免疫微环境的关系

doi:10.12280/gjfckx.20251496

摘要/Abstract

摘要：

目的：基于多组学数据库系统分析角蛋白18（keratin 18，KRT18）在卵巢癌中的表达特征及其与患者生存和肿瘤免疫微环境的关系。方法：整合癌症基因组图谱（The Cancer Genome Atlas，TCGA）、GTEx、GEO（GSE66957）数据库转录组数据分析KRT18 mRNA和基因表达差异，并结合CPTAC蛋白质组数据库及HPA数据库免疫组织化学检查结果验证KRT18蛋白水平。采用Kaplan-Meier Plotter数据库进行生存分析，利用TIMER 3.0分析KRT18基因表达水平与肿瘤免疫细胞浸润的相关性，结合基因集富集分析（gene set enrichment analysis，GSEA）及STRING数据库进行功能富集和蛋白质-蛋白质互作网络分析。通过TISCH2数据库中的单细胞转录组数据分析KRT18基因在不同细胞亚群中的表达分布。结果：卵巢癌组织中KRT18 mRNA、基因及蛋白均显著高于正常卵巢组织（均P<0.05）。生存分析显示KRT18基因高表达组与低表达组的总生存期和无进展生存期差异均无统计学意义（均P>0.05）。KRT18基因表达与M1型及M2型巨噬细胞、中性粒细胞、初始CD8+T细胞、记忆B细胞及未成熟浆细胞浸润水平呈负相关，与初始B细胞浸润水平呈正相关（均P<0.05）。GSEA分析提示其相关通路涉及抗原加工与呈递相关生物过程及小GTP酶信号通路等。单细胞转录组分析显示KRT18基因在恶性肿瘤细胞及成纤维细胞中表达相对较高。结论：KRT18在卵巢癌中稳定高表达，其表达水平与免疫微环境构成存在相关性，提示其可能参与卵巢癌的发生发展过程。

关键词: 角蛋白18, 卵巢肿瘤, 癌, 计算生物学, 免疫, 细胞微环境, 单细胞分析

Abstract:

Objective: To systematically analyze the expression profile of keratin 18 (KRT18) in ovarian cancer and its association with patient survival and tumor immune microenvironment based on multi-omics databases. Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA), GTEx, and GEO (GSE66957) databases were integrated to analyze differential expression of KRT18 mRNA and gene. Protein-level validation was performed using the CPTAC proteomics database and immunohistochemistry results from HPA database. Survival analysis was conducted via the Kaplan-Meier Plotter database. The correlation between KRT18 gene expression and tumor-infiltrating immune cells was analyzed using TIMER 3.0. Functional enrichment and protein-protein interaction network analyses were conducted using gene set enrichment analysis (GSEA) and the STRING database. Expression distribution of KRT18 gene expression across different cellular subpopulations was assessed using single-cell transcriptomic data from TISCH2 database. Results: Both KRT18 mRNA, gene, and protein expression levels were significantly higher in ovarian cancer tissues compared to normal ovarian tissues (all P<0.05). Survival analysis showed no statistically significant differences in overall survival and progression free survival between the high- and low-expression groups of the KRT18 gene (all P>0.05). KRT18 gene expression was negatively correlated with the infiltration levels of M1- and M2-type macrophages, neutrophils, na?ve CD8+T cells, memory B cells, and immature plasma cells, and positively correlated with the infiltration level of na?ve B cells (all P<0.05). GSEA indicated that KRT18-related pathways were mainly enriched in antigen processing and presentation-related biological processes, as well as small GTPase signaling pathways. Single-cell transcriptomic analysis showed relatively higher expression of the KRT18 gene in malignant tumor cells and fibroblasts. Conclusions: KRT18 is stably overexpressed in ovarian cancer, and its expression level correlated with the composition of the immune microenvironment, suggesting its potential involvement in ovarian carcinogenesis and progression.

Key words: Keratin-18, Ovarian neoplasms, Carcinoma, Computational biology, Immunity, Cellular microenvironment, Single-cell analysis

王居鹏, 任丽, 马明坤, 赵然, 温学红. 角蛋白18在卵巢癌中的表达特征及其与患者生存和肿瘤免疫微环境的关系[J]. 国际妇产科学杂志, 2026, 53(2): 211-219.

WANG Ju-peng, REN Li, MA Ming-kun, ZHAO Ran, WEN Xue-hong. Expression Characteristics of KRT18 in Ovarian Cancer and Its Association with Patient Survival and Tumor Immune Microenvironment[J]. Journal of International Obstetrics and Gynecology, 2026, 53(2): 211-219.

图/表 8

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分析方法	方向	通路名称	NES	P	FDR
GO-BP	激活	外源性肽抗原的加工与呈递	2.528	0.001 3	0.017 3
		经MHCⅡ类分子介导的外源性肽抗原的加工与呈递	2.509	0.001 4	0.017 3
		外源性抗原的加工与呈递	2.469	0.001 3	0.017 3
		经MHCⅡ类分子介导的肽或多糖抗原的加工与呈递	2.460	0.001 4	0.017 3
		小GTPase介导的信号转导调控	2.390	0.001 0	0.017 3
	抑制	嗅觉感知	-3.886	0.041 7	0.120 3
		γ-氨基丁酸信号通路	-2.241	0.003 6	0.022 2
		味觉感知中化学刺激检测	-2.154	0.004 2	0.024 4
		神经元命运决定	-2.093	0.002 9	0.019 3
		G蛋白偶联受体信号通路（偶联环核苷酸第二信使）	-2.015	0.004 9	0.027 3
KEGG	激活	系统性红斑狼疮	2.351	0.001 2	0.008 5
		移植物抗宿主病	2.314	0.001 3	0.008 5
		利什曼原虫感染	2.310	0.001 2	0.008 5
		同种异体移植排斥反应	2.294	0.001 3	0.008 5
		细胞外基质-受体相互作用	2.289	0.001 2	0.008 5
	抑制	嗅觉转导	-4.174	0.034 5	0.077 9
		青少年发病的成人型糖尿病	-2.285	0.003 8	0.017 0
		亚油酸代谢	-2.261	0.003 9	0.017 0
		神经活性配体-受体相互作用	-2.188	0.022 7	0.057 8
		视黄醇的新陈代谢	-1.780	0.009 3	0.031 0

分析方法	方向	通路名称	NES	P	FDR
GO-BP	激活	外源性肽抗原的加工与呈递	2.528	0.001 3	0.017 3
		经MHCⅡ类分子介导的外源性肽抗原的加工与呈递	2.509	0.001 4	0.017 3
		外源性抗原的加工与呈递	2.469	0.001 3	0.017 3
		经MHCⅡ类分子介导的肽或多糖抗原的加工与呈递	2.460	0.001 4	0.017 3
		小GTPase介导的信号转导调控	2.390	0.001 0	0.017 3
	抑制	嗅觉感知	-3.886	0.041 7	0.120 3
		γ-氨基丁酸信号通路	-2.241	0.003 6	0.022 2
		味觉感知中化学刺激检测	-2.154	0.004 2	0.024 4
		神经元命运决定	-2.093	0.002 9	0.019 3
		G蛋白偶联受体信号通路（偶联环核苷酸第二信使）	-2.015	0.004 9	0.027 3
KEGG	激活	系统性红斑狼疮	2.351	0.001 2	0.008 5
		移植物抗宿主病	2.314	0.001 3	0.008 5
		利什曼原虫感染	2.310	0.001 2	0.008 5
		同种异体移植排斥反应	2.294	0.001 3	0.008 5
		细胞外基质-受体相互作用	2.289	0.001 2	0.008 5
	抑制	嗅觉转导	-4.174	0.034 5	0.077 9
		青少年发病的成人型糖尿病	-2.285	0.003 8	0.017 0
		亚油酸代谢	-2.261	0.003 9	0.017 0
		神经活性配体-受体相互作用	-2.188	0.022 7	0.057 8
		视黄醇的新陈代谢	-1.780	0.009 3	0.031 0