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Interleukin 20 receptor subunit beta (IL20RB) predicts poor prognosis and regulates immune cell infiltration in clear cell renal cell carcinoma
BACKGROUND AND OBJECTIVE: Emerging evidence has proven the robust role of tumor mutation burden (TMB) and immune cell infiltration (ICI) in cancer immunotherapy. However, the precise effect of TMB and ICI on clear cell renal cell carcinoma (ccRCC) remains elusive and merits further investigation. Th...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327257/ https://www.ncbi.nlm.nih.gov/pubmed/35883015 http://dx.doi.org/10.1186/s12863-022-01076-4 |
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author | Zhang, Haoxun Liu, Yiwen Wang, Bowen Wang, Chunyang |
author_facet | Zhang, Haoxun Liu, Yiwen Wang, Bowen Wang, Chunyang |
author_sort | Zhang, Haoxun |
collection | PubMed |
description | BACKGROUND AND OBJECTIVE: Emerging evidence has proven the robust role of tumor mutation burden (TMB) and immune cell infiltration (ICI) in cancer immunotherapy. However, the precise effect of TMB and ICI on clear cell renal cell carcinoma (ccRCC) remains elusive and merits further investigation. Therefore, we aim to identify the TMB-related genes in predicting prognosis and to explore the potential mechanisms of the identified Interleukin 20 receptor subunit beta (IL20RB) in ICI in ccRCC. METHOD: The relative information of patients with ccRCC was obtained from The Cancer Genome Atlas database (TCGA). Immune-related genes were downloaded from the Immunology Database and Analysis Portal database. Cox regression analysis was used to identify prognosis-related immune genes for ccRCC. The relationship of IL20RB expression levels with clinicopathological parameters was analyzed using the “limma” and “survival” packages. Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC) databases were used as external validation. Quantitative Real-time PCR (qRT-PCR) and western blots were used to validate the expression levels of IL20RB in tumor cells. Cell counting kit-8 (CCK-8) assay and colony formation assay were used to examine the effect of IL20RB on the viability of ccRCC cells. Gene set enrichment analysis (GSEA) was introduced for the analysis of IL20RB-related signaling pathways. Tumor Immune Estimation Resource (TIMER) and Tumor and Immune System Interaction Database (TISIDB) were utilized to determine the correlation of IL20RB expression levels with tumor-infiltrating immune cells (TIICs). RESULTS: IL20RB was significantly overexpressed in different ccRCC tissues and cells. High IL20RB expression in ccRCC patients was associated with short overall survival, high tumor grade, and advanced TNM stage. After knockdown of IL20RB with small interfering RNA (siRNA) technology, ccRCC cells’ proliferation was significantly attenuated. Moreover, overexpression of IL20RB could increase the infiltration level of several immune cells, especially T follicular helper cells (Tfh), and overexpressed Tfh cells were correlated with poor prognosis in ccRCC. CONCLUSIONS: IL20RB may function as an immune-associated therapeutic target for it determines cancer progression and regulates immune cell infiltration in ccRCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12863-022-01076-4. |
format | Online Article Text |
id | pubmed-9327257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-93272572022-07-28 Interleukin 20 receptor subunit beta (IL20RB) predicts poor prognosis and regulates immune cell infiltration in clear cell renal cell carcinoma Zhang, Haoxun Liu, Yiwen Wang, Bowen Wang, Chunyang BMC Genom Data Research BACKGROUND AND OBJECTIVE: Emerging evidence has proven the robust role of tumor mutation burden (TMB) and immune cell infiltration (ICI) in cancer immunotherapy. However, the precise effect of TMB and ICI on clear cell renal cell carcinoma (ccRCC) remains elusive and merits further investigation. Therefore, we aim to identify the TMB-related genes in predicting prognosis and to explore the potential mechanisms of the identified Interleukin 20 receptor subunit beta (IL20RB) in ICI in ccRCC. METHOD: The relative information of patients with ccRCC was obtained from The Cancer Genome Atlas database (TCGA). Immune-related genes were downloaded from the Immunology Database and Analysis Portal database. Cox regression analysis was used to identify prognosis-related immune genes for ccRCC. The relationship of IL20RB expression levels with clinicopathological parameters was analyzed using the “limma” and “survival” packages. Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC) databases were used as external validation. Quantitative Real-time PCR (qRT-PCR) and western blots were used to validate the expression levels of IL20RB in tumor cells. Cell counting kit-8 (CCK-8) assay and colony formation assay were used to examine the effect of IL20RB on the viability of ccRCC cells. Gene set enrichment analysis (GSEA) was introduced for the analysis of IL20RB-related signaling pathways. Tumor Immune Estimation Resource (TIMER) and Tumor and Immune System Interaction Database (TISIDB) were utilized to determine the correlation of IL20RB expression levels with tumor-infiltrating immune cells (TIICs). RESULTS: IL20RB was significantly overexpressed in different ccRCC tissues and cells. High IL20RB expression in ccRCC patients was associated with short overall survival, high tumor grade, and advanced TNM stage. After knockdown of IL20RB with small interfering RNA (siRNA) technology, ccRCC cells’ proliferation was significantly attenuated. Moreover, overexpression of IL20RB could increase the infiltration level of several immune cells, especially T follicular helper cells (Tfh), and overexpressed Tfh cells were correlated with poor prognosis in ccRCC. CONCLUSIONS: IL20RB may function as an immune-associated therapeutic target for it determines cancer progression and regulates immune cell infiltration in ccRCC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12863-022-01076-4. BioMed Central 2022-07-26 /pmc/articles/PMC9327257/ /pubmed/35883015 http://dx.doi.org/10.1186/s12863-022-01076-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Zhang, Haoxun Liu, Yiwen Wang, Bowen Wang, Chunyang Interleukin 20 receptor subunit beta (IL20RB) predicts poor prognosis and regulates immune cell infiltration in clear cell renal cell carcinoma |
title | Interleukin 20 receptor subunit beta (IL20RB) predicts poor prognosis and regulates immune cell infiltration in clear cell renal cell carcinoma |
title_full | Interleukin 20 receptor subunit beta (IL20RB) predicts poor prognosis and regulates immune cell infiltration in clear cell renal cell carcinoma |
title_fullStr | Interleukin 20 receptor subunit beta (IL20RB) predicts poor prognosis and regulates immune cell infiltration in clear cell renal cell carcinoma |
title_full_unstemmed | Interleukin 20 receptor subunit beta (IL20RB) predicts poor prognosis and regulates immune cell infiltration in clear cell renal cell carcinoma |
title_short | Interleukin 20 receptor subunit beta (IL20RB) predicts poor prognosis and regulates immune cell infiltration in clear cell renal cell carcinoma |
title_sort | interleukin 20 receptor subunit beta (il20rb) predicts poor prognosis and regulates immune cell infiltration in clear cell renal cell carcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327257/ https://www.ncbi.nlm.nih.gov/pubmed/35883015 http://dx.doi.org/10.1186/s12863-022-01076-4 |
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