Claudin-6 is a single prognostic marker and functions as a tumor-promoting gene in a subgroup of intestinal type gastric cancer

Kohmoto, Tomohiro; Masuda, Kiyoshi; Shoda, Katsutoshi; Takahashi, Rizu; Ujiro, Sae; Tange, Shoichiro; Ichikawa, Daisuke; Otsuji, Eigo; Imoto, Issei

doi:10.1007/s10120-019-01014-x

Cited by 35 publications

(33 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…one report indicated that the expression of cldn6 differed between gastric cancer and adjacent tissues (36). additional studies showed that cldn6 expression differed in gastric cancer compared with healthy tissue (37)(38)(39)(40)(41), and according to Zavala-Zendejas et al (37), the expression of cldn6 in gastric cancer tissues was higher compared with that in adjacent tissues. cldn6 is a gene promoter in gastric cancer, and its upregulation enhances the tumorigenicity of gastric cancer cells (37).…”

Section: Expression and Regulation Mechanisms Of Cldn6 In Tumoursmentioning

confidence: 98%

Claudin 6: Therapeutic prospects for tumours, and mechanisms of expression and regulation (Review)

Yang

Fan

et al. 2021

Mol Med Rep

View full text Add to dashboard Cite

Tight junctions (TJs) are an important component of cell connectivity; they maintain cell polarity, permeability and adhesion, and participate in the regulation of cell proliferation and differentiation. The claudin (cldn) family is integral to TJs, and cldn6 is an important member of this family. abnormal expression of cldn6 can destroy the integrity of TJs through various mechanisms and can serve multiple roles in the occurrence and development of tumours. cldn6 is widely expressed in various tumours but rarely expressed in healthy adult tissues. The aim of this review is to critically examine the recent literature on cldn6, including its structure, expression in different tumours, regulatory mechanisms and therapeutic prospects. although some conclusions are controversial, in certain tumours, such as liver, ovarian, endometrial and oesophageal cancer, and atypical teratoid/rhabdoid tumours, research consistently shows that cldn6 is expressed in tumour tissues but is not expressed or is expressed at low levels in surrounding tissues. in these tumours, cldn6 has potential as a carcinoembryonic antigen and a therapeutic target. Contents1. introduction 2. Structural characteristics of cldn6 3. expression and regulation mechanisms of cldn6 in tumours 4. cldn6 and drug resistance in cancer 5. Prospect of cldn6 in the treatment of tumours 6. discussion conclusionHuan du 1,2 , XiYue YanG 2 , JinJia Fan 2 and XiaoBo du 1

show abstract

Section: Expression and Regulation Mechanisms Of Cldn6 In Tumoursmentioning

confidence: 98%

Claudin 6: Therapeutic prospects for tumours, and mechanisms of expression and regulation (Review)

Yang

Fan

et al. 2021

Mol Med Rep

View full text Add to dashboard Cite

show abstract

“…As for the genomic analysis, 40% of diffused-type GC was associated with CHD1 (chromodomain-helicase DNA-binding protein 1) loss; additionally, diffused-type GC was inclined to have mutant p53 and oncoprotein Her2, which induced diffused-type GC to be more aggressive type ( 13 ). However, other genes that were overexpressed in intestinal-type GC were also associated with poorer survival such as Claudin 6 (CLDN6) ( 14 ). There was little literature to investigate the difference of prognosis for patients with intestinal-type and diffused-type GC.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Incidence and Survival of Gastric Cancer Based on the Lauren Classification: A Large Population-Based Study Using SEER

et al. 2020

View full text Add to dashboard Cite

Background: Limited evidence exists on the incidence of gastric cancer (GC), and contradictory results exist for the prognosis of GC based on the Lauren classification. We analyzed the incidence and survival of GC based on the Lauren classification. Methods: The Surveillance, Epidemiology, and End Results (SEER) database from 1975 through 2015 was used to identify all patients with surgically resected, histologically diagnosed intestinal or diffused-type GC. Propensity score matching was used to analyze the association between the Lauren classification type and prognosis. Results: The trend of total GC incidence showed an obvious decrease (APC = −1.51, 95% CI: −2.31 to −1.01) as well as that of the intestinal type (APC = −1.43, 95% CI: −2.01 to −1.12). However, we found that the relative incidence of the diffused type was increased (APC = 0.6, 95% CI: 0.41–0.82). The trend of the total incidence of GC (APC = −1.31, 95% CI: −1.91 to −1.03) and that of the intestinal type (APC = −1.11, 95% CI: −1.53 to −0.98) was decreased in 40–49-year-olds, but that of the diffused type was increased (APC = 1.5, 95% CI: 1.2–1.72). We found that trends in GC incidence exhibited a similar pattern in the regional and distant stages and showed a decrease from 1975 through 2015. However, the incidence rate of the local stage was increased, with an APC of 0.5 (95% CI: 0.3–0.7). We identified 15,989 GC cases from the SEER database, including 13,852 intestinal-type and 2,138 diffused-type cases. The 1,336 intestinal-type cases were matched with 1,336 diffused-type cases using propensity score matching (PSM), and patients with the diffused type had a better prognosis than patients with the intestinal type (HR = 0.56, 95% CI: 0.45–0.78). However, we found that patients with diffused-type GC had worse survival than patients with intestinal-type GC in the cohort from Renji Hospital ( P < 0.001). Conclusion: The total incidence of GC and that of the intestinal-type GC decreased, but the incidence of diffused-type GC increased in 40–49-year-olds. Diffused types of GCs may have a different prognosis compared to intestinal-type GCs in different patient cohorts. Nevertheless, these results should be interpreted with caution in assessing the prognosis in combination with other factors.

show abstract

“…CLDN6 had been demonstrated abnormal expression and can be a prognostic marker in cancers including ovarian cancer ( Wang et al, 2013 ), endometrial cancer ( Kojima et al, 2020 ), gastric cancer ( Kohmoto et al, 2020 ), breast carcinoma ( Liu et al, 2016 ; Jia et al, 2019 ), and lung cancer ( Micke et al, 2014 ). Bioinformatic analysis has revealed that CLDN6 is regulated by a diverse set of transcription factors and promotes cancer cell behavior via the ASK1-p38/JNK MAPK secretory signaling pathway ( Lin et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

Claudin-6 is a single prognostic marker and functions as a tumor-promoting gene in a subgroup of intestinal type gastric cancer

Cited by 35 publications

References 47 publications

Claudin 6: Therapeutic prospects for tumours, and mechanisms of expression and regulation (Review)

Claudin 6: Therapeutic prospects for tumours, and mechanisms of expression and regulation (Review)

Analysis of the Incidence and Survival of Gastric Cancer Based on the Lauren Classification: A Large Population-Based Study Using SEER

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

Contact Info

Product

Resources

About