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

Abstract

BackgroundThe 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.MethodsThe 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).ResultsClaudin 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.ConclusionOur 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.

Immunotherapy for Ovarian Cancer: Disappointing or Promising?

“…Its expression is high in fetal tissues but absent in normal adult tissues. However, CLDN6 expression levels are often elevated in several types of human cancers, including testicular, ovarian, cervical, and lung adenocarcinomas . CLDN6 is a highly suitable target for tumor cells and is an ideal candidate for CAR-T therapy due to its consistent expression profile.…”

“…However, CLDN6 expression levels are often elevated in several types of human cancers, including testicular, ovarian, cervical, and lung adenocarcinomas. 102 CLDN6 is a highly suitable target for tumor cells and is an ideal candidate for CAR-T therapy due to its consistent expression profile. In a study, researchers found that CLDN6-CAR-T effectively eliminated CLDN6-expressing PA-1 ovarian cancers.…”

CLDN6: From Traditional Barrier Function to Emerging Roles in Cancers

“…Studies have shown that CLDN6 inhibits the development and progression in some cancers such as breast cancer [22,24,[61][62][63], cervical cancer [56], and meningioma [64]. In hepatocellular cancer [50,65,66], gastric cancer [52,67], endometrial cancer [68,69], and ovarian cancer [70], CLDN6 has the opposite roles. The oncogenic role or conversely tumor-suppressive effect of CLDN6 in different types of cancer is shown in Table 2.…”

Independent prognostic value of CLDN6 in bladder cancer based on M2 macrophages related signature

“… 14 , 15 In addition, CLDN6 has been found to be associated with immune infiltration in ovarian cancer. 16 However, the evidence linking CLDN6 to M2 macrophages in bladder cancer is still insufficient.…”