Expression of CLDN6 in tissues of gastric cancer patients: Association with clinical pathology and prognosis

Gao, Fangmei; Li, Ming-Dong; Xiang, Rui; Zhou, Xin; Zhu, Lianying; Zhai, Yi

doi:10.3892/ol.2019.10129

Cited by 23 publications

(23 citation statements)

References 22 publications

(21 reference statements)

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“…However, current studies indicate that some members of the claudin family, such as CLDN4 [48] and CLDN1 [49], play an oncogenic role in some types of tumours. Furthermore, as a member of the claudin family, the function of CLDN6 varies among different types of tumours [50,51]. In hepatocellular carcinoma, CLDN6 is highly expressed and associated with poor prognosis (unpublished research by our group).…”

Section: Discussionmentioning

confidence: 98%

A SUMOylation-dependent HIF-1α/CLDN6 negative feedback mitigates hypoxia-induced breast cancer metastasis

Jia

Guo

Qiu

et al. 2020

J Exp Clin Cancer Res

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Background: We have previously described CLDN6 as a tumor suppressor gene in breast cancer. Here, a new finding is that CLDN6 was upregulated under hypoxia, a commonly recognized factor that promotes tumor metastasis. In this study, we aim to explain this confusing finding and delineate the role of CLDN6 in the breast cancer metastasis induced by hypoxia. Methods: RNAi and ChIP assays were used to confirm that CLDN6 is transcriptional regulated by HIF-1α. mRNA seq and KEGG analysis were performed to define the downstream pathways of CLDN6. The roles of the CLDN6/SENP1/ HIF-1α signaling on tumor metastasis were evaluated by function experiments and clinical samples. Finally, the possible transcription factor of SENP1 was suspected and then validated by ChIP assay. Results: We demonstrated a previously unrecognized negative feedback loop exists between CLDN6 and HIF-1α. CLDN6 was transcriptionally up-regulated by HIF-1α under hypoxia. On the other hand, in cytoplasm CLDN6 combines and retains β-catenin, a transcription factor of SENP1, causing β-catenin degradation and preventing its nuclear translocation. This process reduced SENP1 expression and prevented the deSUMOylation of HIF-1α, ultimately leading to HIF-1α degradation and breast cancer metastasis suppression. Conclusions: Our data provide a molecular mechanistic insight indicating that CLDN6 loss may lead to elevated HIF-1α-driven breast cancer metastasis in a SUMOylation-dependent manner.

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Section: Discussionmentioning

confidence: 98%

A SUMOylation-dependent HIF-1α/CLDN6 negative feedback mitigates hypoxia-induced breast cancer metastasis

Jia

Guo

Qiu

et al. 2020

J Exp Clin Cancer Res

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“…And Zhang et al revealed that upregulated HIF3A expression promotes the progression of ovarian cancer (57). CLDN6 has a lower expression level in gastric cancer patients and is associated with age, distant metastasis, lymph node metastasis, and pathological staging showing as a potential biomarker (58). ACTL8 plays a key role in the metastasis, invasion, and poor prognosis of colorectal cancer (59).…”

Section: Discussionmentioning

confidence: 99%

Analysis of tumor mutation burden combined with immune infiltrates in endometrial cancer

Zhang¹,

An²,

Zhou³

et al. 2021

Ann Transl Med

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Background: Tumor mutational burden (TMB) is widely regarded as a predictor of response to immunotherapy. Few researchers have focused on the activity and prognosis of TMB in endometrial cancer (EC) and immune cells. Our study aimed to identify the prognostic role of TMB in EC.Methods: We downloaded transcriptome data from The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analysis with log-rank test was conducted to assess the difference in overall survival (OS) between the high and low TMB groups. The "CIBERSORT" scripts were performed to evaluate the immune compositions of EC patients. Cox regression analysis and survival analysis were used to verify the prognostic value prognosis of TMB.Results: We obtained the single nucleotide mutation data for 529 EC patients. A missense mutation was the most common mutation type. TMB was associated with survival outcome, tumor grades, and pathological types. We identified 10 hub TMB-related signature and found that elevated T-cell subsets infiltrating density in the high TMB group revealed improved survival outcomes. According to Kaplan-Meier analysis, T cells gamma delta and T cells regulatory were prognostic immune cells in EC samples. Moreover, many top gene set enrichment analysis (GSEA) results, including amino sugar and nucleotide sugar metabolism, nucleotide excision repair, or p53 signaling pathway, were enriched significantly with TMB level as phenotype.Conclusions: TMB is an important prognostic factor for EC, and TMB-related genes may be potential therapeutic targets for EC.

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“…Results contrary to findings of the present study have been reported for GC as well as several other types of cancers. In GC (1) lower CLDN6 protein [34] and mRNA [35] levels in tumors as compared with non-tumorous tissues, (2) an association of lower CLDN6 mRNA expression in tumors with worse prognosis [35], and (3) an increased CLDN6 protein expression in both intestinal and diffuse types [36] have been reported. In breast cancer patients, tumor-specific downregulation of CLDN6 expression and its association with lymphatic metastasis have also been noted [37].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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Background We aimed to identify novel tumor-promoting drivers highly expressed in gastric cancer (GC) that contribute to worsened prognosis in affected patients. Methods Genes whose expression was increased and correlated with worse prognosis in GC were screened using datasets from the Cancer Genome Atlas and Gene Expression Omnibus. We examined Claudin-6 (CLDN6) immunoreactivity in GC tissues and the effect of CLDN6 on cellular functions in GC cell lines. The mechanisms underlying GC-promoting function of CLDN6 were also investigated. Results CLDN6 was identified as a gene overexpressed in GC tumors as compared with adjacent non-tumorous tissues and whose increased expression was positively correlated with worse overall survival of GC patients, particularly those with Lauren's intestinal type GC, in data from multiple publicly available datasets. Additionally, membranous CLDN6 immunoreactivity detected in intestinal type GC tumors was correlated with worse overall survival. In CLDN6-expressing GC cells, silencing of CLDN6 inhibited cell proliferation and migration/invasion abilities, possibly via suppressing transcription of YAP1 and its downstream transcriptional targets at least in part. Conclusions This study identified CLDN6 as a GC-promoting gene, suggesting that CLDN6 to be a possible single prognostic marker and promising therapeutic target for a subset of GC patients.

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Expression of CLDN6 in tissues of gastric cancer patients: Association with clinical pathology and prognosis

Cited by 23 publications

References 22 publications

A SUMOylation-dependent HIF-1α/CLDN6 negative feedback mitigates hypoxia-induced breast cancer metastasis

A SUMOylation-dependent HIF-1α/CLDN6 negative feedback mitigates hypoxia-induced breast cancer metastasis

Analysis of tumor mutation burden combined with immune infiltrates in endometrial cancer

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

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