{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["15(4)"],"submitter":["Ji HC"],"pubmed_abstract":["<h4>Background</h4>The clinical role of claudin 8 (<i>CLDN8</i>) in kidney renal clear cell carcinoma (KIRC) remains unclarified. Herein, the expression level and potential molecular mechanisms of <i>CLDN8</i> underlying KIRC were determined.<h4>Methods</h4>High-throughput datasets of KIRC were collected from GEO, ArrayExpress, SRA, and TCGA databases to determine the mRNA expression level of the <i>CLDN8</i>. 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 <i>CLDN8</i>. A clustered regularly interspaced short palindromic repeats knockout screen analysis was executed to assess the growth impact of <i>CLDN8</i>. 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.<h4>Results</h4>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). <i>CLDN8</i> downregulation was also confirmed at the single-cell level. Knocking out <i>CLDN8</i> stimulated KIRC cell proliferation. Lower <i>CLDN8</i> expression was correlated with worse overall survival of KIRC patients (hazard ratio of <i>CLDN8</i> downregulation = 1.69, 95% CI: 1.2 - 2.4). Functional pathways associated with <i>CLDN8</i> co-expressed genes were centered on carbon metabolism obstruction, with key hub genes <i>ACADM</i>, <i>ACO2</i>, <i>NDUFS1</i>, <i>PDHB</i>, <i>SDHD</i>, <i>SUCLA2</i>, <i>SUCLG1</i>, and <i>SUCLG2.</i><h4>Conclusions</h4><i>CLDN8</i> is downregulated in KIRC and is considered a potential tumor suppressor. <i>CLDN8</i> deficiency may promote the initiation and progression of KIRC, potentially in conjunction with metabolic dysfunction."],"journal":["World journal of oncology"],"pagination":["662-674"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11236366"],"repository":["biostudies-literature"],"pubmed_title":["Significance and Possible Biological Mechanism for <i>CLDN8</i> Downregulation in Kidney Renal Clear Cell Carcinoma Tissues."],"pmcid":["PMC11236366"],"pubmed_authors":["Li JD","Li SH","Qin K","Zhao CY","Chen G","Zhang GL","Huang ZG","Long Y","Ma YL","Tang YX","Cheng JW","Qin B","Ji HC"],"additional_accession":[]},"is_claimable":false,"name":"Significance and Possible Biological Mechanism for <i>CLDN8</i> Downregulation in Kidney Renal Clear Cell Carcinoma Tissues.","description":"<h4>Background</h4>The clinical role of claudin 8 (<i>CLDN8</i>) in kidney renal clear cell carcinoma (KIRC) remains unclarified. Herein, the expression level and potential molecular mechanisms of <i>CLDN8</i> underlying KIRC were determined.<h4>Methods</h4>High-throughput datasets of KIRC were collected from GEO, ArrayExpress, SRA, and TCGA databases to determine the mRNA expression level of the <i>CLDN8</i>. 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 <i>CLDN8</i>. A clustered regularly interspaced short palindromic repeats knockout screen analysis was executed to assess the growth impact of <i>CLDN8</i>. 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.<h4>Results</h4>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). <i>CLDN8</i> downregulation was also confirmed at the single-cell level. Knocking out <i>CLDN8</i> stimulated KIRC cell proliferation. Lower <i>CLDN8</i> expression was correlated with worse overall survival of KIRC patients (hazard ratio of <i>CLDN8</i> downregulation = 1.69, 95% CI: 1.2 - 2.4). Functional pathways associated with <i>CLDN8</i> co-expressed genes were centered on carbon metabolism obstruction, with key hub genes <i>ACADM</i>, <i>ACO2</i>, <i>NDUFS1</i>, <i>PDHB</i>, <i>SDHD</i>, <i>SUCLA2</i>, <i>SUCLG1</i>, and <i>SUCLG2.</i><h4>Conclusions</h4><i>CLDN8</i> is downregulated in KIRC and is considered a potential tumor suppressor. <i>CLDN8</i> deficiency may promote the initiation and progression of KIRC, potentially in conjunction with metabolic dysfunction.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2026-06-01T07:03:09.536Z","creation":"2026-04-08T10:17:13.303Z"},"accession":"S-EPMC11236366","cross_references":{"pubmed":["38993257"],"doi":["10.14740/wjon1869"]}}