&lt;p&gt;Prognostic Value and Potential Biological Functions of CLDN8 in Patients with Clear Cell Renal Cell Carcinoma&lt;/p&gt;

Zhu, Zhenpeng; Xu, Chunru; Lin, Lanruo; Lv, Tianjing; Cai, Tianyu; Jian, Lin

doi:10.2147/ott.s266846

Cited by 8 publications

(9 citation statements)

References 29 publications

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“…It has been reported that CLDN8 could serve as an independent prognostic factor in ccRCC, in which it suppresses 786–O proliferation, migration, and invasion through the EMT and AKT pathways. 36 This finding is consistent with the results of our analysis. The Kaplan-Meier Plotter database was used to analyze the effects of CLDN7, 8, 10, 11, 14, 16, and 19 on the survival rate of patients with ccRCC.…”

Section: Discussionsupporting

confidence: 93%

Comprehensive analysis of the expression and prognosis value of claudin family members in clear cell renal cell carcinoma

Dang

et al. 2023

Eur J Inflamm

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Objective: Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all renal cancers and has a poor prognosis. Studies have found that the abnormal expression of claudins (CLNDs) can influence the functions of tight junctions (TJs) and plays an important role in the occurrence, development, and metastasis of malignant tumours in a variety of epithelial malignant tumours. However, the roles of the different CLNDs in ccRCC are poorly understood. Methods: Used the GEPIA, UALCAN, HPA, Kaplan-Meier Plotter, cBioPortal, String-DB, GeneMANIA, Metascape, and TIMER databases to collect data. Results: The expression levels of CLDN7, 8, 10, 11, 14, 16, and 19 were significantly reduced and promoters were hypermethylated in ccRCC-affected tissues. ccRCC patients with low expression levels are associated highly with the clinical cancer stages, tumour grades, and poor overall survival. Protein interaction and enrichment analysis showed the differential expressions of CLDNs were primarily associated with epithelial cell differentiation and regulation of cell adhesion. Moreover, differential expressions of CLDNs were significantly correlated with the infiltration of diverse immune cells, including six types of CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells in ccRCC. Conclusion: They are expected to serve as biomarkers for predicting the prognosis of ccRCC patients.

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Section: Discussionsupporting

confidence: 93%

Comprehensive analysis of the expression and prognosis value of claudin family members in clear cell renal cell carcinoma

Dang

et al. 2023

Eur J Inflamm

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“…The MAPK/ERK signaling pathway is activated in colorectal cancers when CLDN8 is overexpressed ( Cheng et al, 2019 ). In contrast, low levels of CLDN8 expression slow the progression of renal clear cell carcinoma via the EMT/AKT signaling pathway ( Zhu et al, 2020 ). Colonic epithelial barrier function in mice is influenced by TGF family signaling, which regulates CLDN2, CLDN4, CLDN7, and CLDN8 in colonic epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Prognostic Relevance of Differential Claudin Gene Expression Highlights Claudin-4 as Being Suppressed by TGFβ1 Inhibitor in Colorectal Cancer

Yang

Zhang

et al. 2022

Front. Genet.

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Background: Claudins (CLDNs) are a family of closely related transmembrane proteins that have been linked to oncogenic transformation and metastasis across a range of cancers, suggesting that they may be valuable diagnostic and/or prognostic biomarkers that can be used to evaluate patient outcomes. However, CLDN expression patterns associated with colorectal cancer (CRC) remain to be defined.Methods: The mRNA levels of 21 different CLDN family genes were assessed across 20 tumor types using the Oncomine database. Correlations between these genes and patient clinical outcomes, immune cell infiltration, clinicopathological staging, lymph node metastasis, and mutational status were analyzed using the GEPIA, UALCAN, Human Protein Atlas, Tumor Immune Estimation Resource, STRING, Genenetwork, cBioportal, and DAVID databases in an effort to clarify the potential functional roles of different CLDN protein in CRC. Molecular docking analyses were used to probe potential interactions between CLDN4 and TGFβ1. Levels of CLDN4 and CLDN11 mRNA expression in clinical CRC patient samples and in the HT29 and HCT116 cell lines were assessed via qPCR. CLDN4 expression levels in these 2 cell lines were additionally assessed following TGFβ1 inhibitor treatment.Results: These analyses revealed that COAD and READ tissues exhibited the upregulation of CLDN1, CLDN2, CLDN3, CLDN4, CLDN7, and CLDN12 as well as the downregulation of CLDN5 and CLDN11 relative to control tissues. Higher CLDN11 and CLDN14 expression as well as lower CLDN23 mRNA levels were associated with poorer overall survival (OS) outcomes. Moreover, CLDN2 and CLDN3 or CLDN11 mRNA levels were significantly associated with lymph node metastatic progression in COAD or READ lower in COAD and READ tissues. A positive correlation between the expression of CLDN11 and predicted macrophage, dendritic cell, and CD4+ T cell infiltration was identified in CRC, with CLDN12 expression further being positively correlated with CD4+ T cell infiltration whereas a negative correlation was observed between such infiltration and the expression of CLDN3 and CLDN15. A positive correlation between CLDN1, CLDN16, and neutrophil infiltration was additionally detected, whereas neutrophil levels were negatively correlated with the expression of CLDN3 and CLDN15. Molecular docking suggested that CLDN4 was able to directly bind via hydrogen bond with TGFβ1. Relative to paracancerous tissues, clinical CRC tumor tissue samples exhibited CLDN4 and CLDN11 upregulation and downregulation, respectively. LY364947 was able to suppress the expression of CLDN4 in both the HT29 and HCT116 cell lines.Conclusion: Together, these results suggest that the expression of different CLDN family genes is closely associated with CRC tumor clinicopathological staging and immune cell infiltration. Moreover, CLDN4 expression is closely associated with TGFβ1 in CRC, suggesting that it and other CLDN family members may represent viable targets for antitumor therapeutic intervention.

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“…Similar to claudin-7, claudin-8 exhibits membranous staining patterns in the distal tubules and collecting ducts ( Lechpammer et al, 2008 ). Clear cell RCCs exhibit lower claudin-8 mRNA and protein levels than normal tissue samples ( Zhu et al, 2020 ). The protein appears to play a role in facilitating pro-neoplastic effects.…”

Section: Aberrant Expression Of Claudins In Renal Cell Carcinomasmentioning

confidence: 99%

Claudins in genitourinary tract neoplasms: mechanisms, prognosis, and therapeutic prospects

Arabi,

Fawzy,

Sabbah

et al. 2023

Front. Cell Dev. Biol.

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Genitourinary (GU) cancers are among the most prevalent neoplasms in the world, with bladder cancers constituting 3% of global cancer diagnoses. However, several pathogenetic mechanisms remain controversial and unclear. Claudins, for example, have been shown to play a significant role in several cancers of the human body. Their role in GU cancers has not been extensively studied. Aberrant expression of claudins −1, −2, −3, −4, −7, and −11 has been expressed in urothelial cell carcinomas. In prostate cancers, altered levels of claudins −1, −2, −3, −4, and −5 have been reported. Furthermore, the levels of claudins −1, −2, −3, −4, −6, −7, −8, and −10 have been studied in renal cell carcinomas. Specifically, claudins −7 and −8 have proven especially useful in differentiating between chromophobe renal cell carcinomas and oncocytomas. Several of these claudins also correlate with clinicopathologic parameters and prognosis in GU cancers. Although mechanisms underpinning aberrant expression of claudins in GU cancers are unclear, epigenetic changes, tumor necrosis factor-ɑ, and the p63 protein have been implicated. Claudins also provide therapeutic value through tailored immunotherapy via molecular subtyping and providing therapeutic targets, which have shown positive outcomes in preclinical studies. In this review, we aim to summarize the literature describing aberrant expression of claudins in urothelial, prostatic, and renal cell carcinomas. Then, we describe the mechanisms underlying these changes and the therapeutic value of claudins. Understanding the scope of claudins in GU cancers paves the way for several diagnostic, prognostic, and therapeutic innovations.

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<p>Prognostic Value and Potential Biological Functions of CLDN8 in Patients with Clear Cell Renal Cell Carcinoma</p>

Cited by 8 publications

References 29 publications

Comprehensive analysis of the expression and prognosis value of claudin family members in clear cell renal cell carcinoma

Comprehensive analysis of the expression and prognosis value of claudin family members in clear cell renal cell carcinoma

Evaluation of the Prognostic Relevance of Differential Claudin Gene Expression Highlights Claudin-4 as Being Suppressed by TGFβ1 Inhibitor in Colorectal Cancer

Claudins in genitourinary tract neoplasms: mechanisms, prognosis, and therapeutic prospects

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