Significance and Possible Biological Mechanism for Downregulation in Kidney Renal Clear Cell Carcinoma Tissues

Overview

Journal World J Oncol

Specialty Oncology

Date 2024 Jul 12

PMID 38993257

Authors

Han Chu Ji

Jian Di Li

Guan Lan Zhang

Zhi Guang Huang

Ji Wen Cheng

Sheng Hua Li

Chun Yan Zhao

Yu Xing Tang

Kai Qin

You Liang Ma

Yu Long

Gang Chen

Bin Qin

Affiliations

Soon will be listed here.

Abstract

Background: The clinical role of claudin 8 () in kidney renal clear cell carcinoma (KIRC) remains unclarified. Herein, the expression level and potential molecular mechanisms of underlying KIRC were determined.

Methods: High-throughput datasets of KIRC were collected from GEO, ArrayExpress, SRA, and TCGA databases to determine the mRNA expression level of the . In-house tissue microarrays and immunochemistry were performed to examine CLDN8 protein expression. A summary receiver operating characteristic curve (SROC) and standardized mean difference (SMD) forest plot were generated using Stata v16.0. Single-cell analysis was conducted to further prove the expression level of . A clustered regularly interspaced short palindromic repeats knockout screen analysis was executed to assess the growth impact of . Functional enrichment analysis was conducted using the Metascape database. Additionally, single-sample gene set enrichment analysis was implied to explore immune cell infiltration in KIRC.

Results: A total of 17 mRNA datasets comprising 1,060 KIRC samples and 452 non-cancerous control samples were included in this study. Additionally, 105 KIRC and 16 non-KIRC tissues were analyzed using in-house immunohistochemistry. The combined SMD was -5.25 (95% confidence interval (CI): -6.13 to -4.37), and CLDN8 downregulation yielded an SROC area under the curve (AUC) close to 1.00 (95% CI: 0.99 - 1.00). downregulation was also confirmed at the single-cell level. Knocking out stimulated KIRC cell proliferation. Lower expression was correlated with worse overall survival of KIRC patients (hazard ratio of downregulation = 1.69, 95% CI: 1.2 - 2.4). Functional pathways associated with co-expressed genes were centered on carbon metabolism obstruction, with key hub genes , , , , , , , and

Conclusions: is downregulated in KIRC and is considered a potential tumor suppressor. deficiency may promote the initiation and progression of KIRC, potentially in conjunction with metabolic dysfunction.

Citing Articles

Expression and Targeted Application of Claudins Family in Hepatobiliary and Pancreatic Diseases.

Du F, Xie Y, Wu S, Ji M, Dong B, Zhu C J Hepatocell Carcinoma. 2024; 11:1801-1821.

PMID: 39345937 PMC: 11439345. DOI: 10.2147/JHC.S483861.

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