Down-Regulated CLDN10 Predicts Favorable Prognosis and Correlates With Immune Infiltration in Gastric Cancer

XiongHui Rao; JianLong Jiang; ZhiHao Liang; JianBao Zhang; ZheHong Zhuang; HuaiYu Qiu; Huixing Luo; Nuoqing Weng; Xiaobin Wu

doi:10.3389/fgene.2021.747581

Down-Regulated CLDN10 Predicts Favorable Prognosis and Correlates With Immune Infiltration in Gastric Cancer

Front Genet. 2021 Oct 13:12:747581. doi: 10.3389/fgene.2021.747581. eCollection 2021.

Authors

XiongHui Rao¹, JianLong Jiang², ZhiHao Liang¹, JianBao Zhang¹, ZheHong Zhuang¹, HuaiYu Qiu¹, Huixing Luo¹, Nuoqing Weng¹, Xiaobin Wu¹

Affiliations

¹ Department of Gastrointestinal Surgery, The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
² Department of Gastrointestinal Surgery, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.

Abstract

Background: CLDN10, an important component of the tight junctions of epithelial cells, plays a crucial role in a variety of tumors. The effect of CLDN10 expression in gastric cancer, however, has yet to be elucidated. Methods: Differential expression of CLDN10 at the mRNA and protein levels was evaluated using Oncomine, ULCAN, HPA and TIMER2.0 databases. Real-time polymerase chain reaction (RT-PCR) was utilized to further verify the expression of CLDN10 in vitro. Correlations between CLDN10 expression and clinical outcomes of gastric cancer were explored by Kaplan-Meier Plotter. Gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) were performed via LinkedOmics and GeneMANIA. The correlations between CLDN10 expression and immune cell infiltration and somatic copy number alternations (SCNA) in gastric cancer were explored by TIMER2.0 and GEPIA2.0. Results: CLDN10 expression was lower in gastric cancer compared to adjacent normal tissues, and associated with better prognosis. CLDN10 also showed significant differences at different T stages, Lauren classification, treatments and HER2 status. PPI and GSEA analysis showed that CLDN10 might be involved in signal transmission, transmembrane transport and metabolism. In some major immune cells, low expression of CLDN10 was associated with increased levels of immune cell infiltration. In addition, it was found that different SCNA status in CLDN10 might affect the level of immune cell infiltration. Furthermore, the expression of CLDN10 was significantly associated with the expression of several immune cell markers, especially B cell markers, follicular helper T cell (Tfh) markers and T cell exhaustion markers. Conclusion: Down-regulated CLDN10 was associated with better overall survival (OS) in gastric cancer. And CLDN10 may serve as a potential prognostic biomarker and correlate to immune infiltration levels in gastric cancer.

Keywords: CLDN10; biomarker; gastric cancer; immune-infiltration; prognosis.