CLDN6和CLDN10与卵巢癌免疫微环境的关联：紧密连接蛋白家族研究

Association of CLDN6 and CLDN10 With Immune Microenvironment in Ovarian Cancer: A Study of the Claudin Family.

作者信息

Gao Peipei, Peng Ting, Cao Canhui, Lin Shitong, Wu Ping, Huang Xiaoyuan, Wei Juncheng, Xi Ling, Yang Qin, Wu Peng

机构信息

Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Genet. 2021 Jun 23;12:595436. doi: 10.3389/fgene.2021.595436. eCollection 2021.

DOI:10.3389/fgene.2021.595436

PMID:34249076

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8262617/

Abstract

BACKGROUND

The claudin family is a group of transmembrane proteins related to tight junctions. While their involvement in cancer has been studied extensively, their relationship with the tumor immune microenvironment remains poorly understood. In this research, we focused on genes related to the prognosis of ovarian cancer and explored their relationship with the tumor immune microenvironment.

METHODS

The cBioPortal for Cancer Genomics database was used to obtain the genetic variation pattern of the claudin family in ovarian cancer. The ONCOMINE and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to explore the mRNA expression of claudins in cancers. The prognostic potential of these genes was examined via the Kaplan-Meier plotter. The enrichment of immunological signatures was determined by gene set enrichment analysis (GSEA). The correlations between claudins and the tumor immune microenvironment in ovarian cancer were investigated via the Tumor Immune Estimation Resource (TIMER).

RESULTS

Claudin genes were altered in 363 (62%) of queried patients/samples. Abnormal expression levels of claudins were observed in various cancers. Among them, CLDN3, CLDN4, CLDN6, CLDN10, CLDN15, and CLDN16 were significantly correlated with overall survival in patients with ovarian cancer. GSEA revealed that CLDN6 and CLDN10 were significantly enriched in immunological signatures of B cell, CD4 T cell, and CD8 T cell. Furthermore, CLDN6 and CLDN10 were negatively correlated and positively correlated, respectively, with immune cell infiltration in ovarian cancer. The expression levels of CLDN6 and CLDN10 were also negatively correlated and positively correlated, respectively, with various gene markers of immune cells in ovarian cancer. Thus, CLDN6 and CLDN10 may participate in immune cell infiltration in ovarian cancer, and these mechanisms may be the reason for poor prognosis.

CONCLUSION

Our study showed that CLDN6 and CLDN10 were prognostic biomarkers correlated with the immune microenvironment in ovarian cancer. These results reveal new roles for CLDN6 and CLDN10 as potential therapeutic targets in the treatment of ovarian cancer.

摘要

背景

紧密连接蛋白家族是一组与紧密连接相关的跨膜蛋白。虽然它们在癌症中的作用已得到广泛研究，但其与肿瘤免疫微环境的关系仍知之甚少。在本研究中，我们聚焦于与卵巢癌预后相关的基因，并探索它们与肿瘤免疫微环境的关系。

方法

利用癌症基因组学cBioPortal数据库获取紧密连接蛋白家族在卵巢癌中的基因变异模式。使用ONCOMINE和基因表达谱交互分析（GEPIA）数据库探索紧密连接蛋白在癌症中的mRNA表达。通过Kaplan-Meier绘图仪检验这些基因的预后潜力。通过基因集富集分析（GSEA）确定免疫特征的富集情况。通过肿瘤免疫估计资源（TIMER）研究紧密连接蛋白与卵巢癌肿瘤免疫微环境之间的相关性。

结果

在363例（62%）被查询的患者/样本中，紧密连接蛋白基因发生改变。在多种癌症中观察到紧密连接蛋白的异常表达水平。其中，CLDN3、CLDN4、CLDN6、CLDN10、CLDN15和CLDN16与卵巢癌患者的总生存期显著相关。GSEA显示，CLDN6和CLDN10在B细胞、CD4 T细胞和CD8 T细胞的免疫特征中显著富集。此外，CLDN6和CLDN10分别与卵巢癌中的免疫细胞浸润呈负相关和正相关。CLDN6和CLDN10的表达水平也分别与卵巢癌中免疫细胞的各种基因标志物呈负相关和正相关。因此，CLDN6和CLDN10可能参与卵巢癌中的免疫细胞浸润，而这些机制可能是预后不良的原因。