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

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.

Integrated Analysis of Multi-Omics Alteration, Immune Profile, and Pharmacological Landscape of Pyroptosis-Derived lncRNA Pairs in Gastric Cancer

“…On the other hand, we found that IPS scores representing immune checkpoints were similarly inferior in the high-risk patients. Our findings were consistent with the previous studies (Liu et al, 2020;Rao et al, 2021), which indicate that PLPPS could guide the prognosis of GC patients. Different from the previous study focusing on the prognosis of GC, we further predicted sensitivity to chemotherapeutic agents in high-and low-risk group patients.…”

“…We found that inflammation and immune response-related pathways were particularly scarce in high-risk patients. Interestingly, as reported by Rao et al (2021), "immune desert" tumors indicate adverse clinical outcomes. In addition, numerous studies indicate that high immune cell infiltration in GC patients was associated with a better long-term prognosis (Liu et al, 2020;Akshatha et al, 2021;.…”

Landscapes and mechanisms of CD8+ T cell exhaustion in gastrointestinal cancer

“…CD39 + and CD39 + PD-1 + CD8 + T cells accumulate in the intestinal tissue during inflammation in CD, and the exhaustion of CD39-expressing CD8 + T cells is related to attenuation and remission of disease activity, which agrees with the report that TEX informs the clinical differences in adult onset IBD (147,148). Detailed roles of TEX in IBD deserve further With bioinformatics tools, researchers have identified multiple dysregulated molecules related to TEX and prognosis in GC or CRC tissues, such as CLDN10, C3AR1, ANTXR1, ANXA1, and PDPN (149)(150)(151)(152)(153). However, their exact regulatory mechanisms in T cell exhaustion remain for further validation and investigation.…”

“…With bioinformatics tools, researchers have identified multiple dysregulated molecules related to TEX and prognosis in GC or CRC tissues, such as CLDN10, C3AR1, ANTXR1, ANXA1, and PDPN ( 149 – 153 ). However, their exact regulatory mechanisms in T cell exhaustion remain for further validation and investigation.…”

Claudin-10 overexpression suppresses human clear cell renal cell carcinoma growth and metastasis by regulating ATP5O and causing mitochondrial dysfunction

“…Claudins are the pivotal transmembrane proteins in TJs (tight junctions), and their expression are often reduced and play important roles in ccRCC, including CLDN8 (claudin-8) 11 , CLDN7 (claudin-7) 12 , and CLDN2 (claudin-2) 13 . Previous studies reported that CLDN10 (claudin-10), as a member of the claudins family, played a vital role in different tumors, including hepatocellular carcinoma 14 , papillary thyroid cancer 15 , and gastric cancer 16 . However, there are few studies on the roles of CLDN10 in kidney cancer.…”