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
{"title":"肾脏透明细胞癌组织中 CLDN8 下调的意义和可能的生物学机制","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","doi":"10.14740/wjon1869","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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></p><p><strong>Conclusions: </strong><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.</p>","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236366/pdf/","citationCount":"0","resultStr":"{\"title\":\"Significance and Possible Biological Mechanism for <i>CLDN8</i> Downregulation in Kidney Renal Clear Cell Carcinoma Tissues.\",\"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\",\"doi\":\"10.14740/wjon1869\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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></p><p><strong>Conclusions: </strong><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.</p>\",\"PeriodicalId\":46797,\"journal\":{\"name\":\"World Journal of Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11236366/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Oncology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.14740/wjon1869\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/5 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14740/wjon1869","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/5 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Significance and Possible Biological Mechanism for CLDN8 Downregulation in Kidney Renal Clear Cell Carcinoma Tissues.
Background: The clinical role of claudin 8 (CLDN8) in kidney renal clear cell carcinoma (KIRC) remains unclarified. Herein, the expression level and potential molecular mechanisms of CLDN8 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 CLDN8. 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 CLDN8. A clustered regularly interspaced short palindromic repeats knockout screen analysis was executed to assess the growth impact of CLDN8. 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). CLDN8 downregulation was also confirmed at the single-cell level. Knocking out CLDN8 stimulated KIRC cell proliferation. Lower CLDN8 expression was correlated with worse overall survival of KIRC patients (hazard ratio of CLDN8 downregulation = 1.69, 95% CI: 1.2 - 2.4). Functional pathways associated with CLDN8 co-expressed genes were centered on carbon metabolism obstruction, with key hub genes ACADM, ACO2, NDUFS1, PDHB, SDHD, SUCLA2, SUCLG1, and SUCLG2.
Conclusions: CLDN8 is downregulated in KIRC and is considered a potential tumor suppressor. CLDN8 deficiency may promote the initiation and progression of KIRC, potentially in conjunction with metabolic dysfunction.
期刊介绍：
World Journal of Oncology, bimonthly, publishes original contributions describing basic research and clinical investigation of cancer, on the cellular, molecular, prevention, diagnosis, therapy and prognosis aspects. The submissions can be basic research or clinical investigation oriented. This journal welcomes those submissions focused on the clinical trials of new treatment modalities for cancer, and those submissions focused on molecular or cellular research of the oncology pathogenesis. Case reports submitted for consideration of publication should explore either a novel genomic event/description or a new safety signal from an oncolytic agent. The areas of interested manuscripts are these disciplines: tumor immunology and immunotherapy; cancer molecular pharmacology and chemotherapy; drug sensitivity and resistance; cancer epidemiology; clinical trials; cancer pathology; radiobiology and radiation oncology; solid tumor oncology; hematological malignancies; surgical oncology; pediatric oncology; molecular oncology and cancer genes; gene therapy; cancer endocrinology; cancer metastasis; prevention and diagnosis of cancer; other cancer related subjects. The types of manuscripts accepted are original article, review, editorial, short communication, case report, letter to the editor, book review.
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