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A comprehensive pancancer analysis reveals the potential value of RAR-related orphan receptor C (RORC) for cancer immunotherapy
Background: RAR-related orphan receptor C (RORC) plays an important role in autoimmune responses and inflammation. However, its function in cancer immunity is still unclear. Its potential value in cancer immunotherapy (CIT) needs to be further studied. Methods: Expression and clinical data for 33 ca...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520743/ https://www.ncbi.nlm.nih.gov/pubmed/36186454 http://dx.doi.org/10.3389/fgene.2022.969476 |
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author | He, Shengfu Yu, Jiawen Sun, Weijie Sun, Yating Tang, Mingyang Meng, Bao Liu, Yanyan Li, Jiabin |
author_facet | He, Shengfu Yu, Jiawen Sun, Weijie Sun, Yating Tang, Mingyang Meng, Bao Liu, Yanyan Li, Jiabin |
author_sort | He, Shengfu |
collection | PubMed |
description | Background: RAR-related orphan receptor C (RORC) plays an important role in autoimmune responses and inflammation. However, its function in cancer immunity is still unclear. Its potential value in cancer immunotherapy (CIT) needs to be further studied. Methods: Expression and clinical data for 33 cancers were obtained from UCSC-Xena. The correlation between RORC expression and clinical parameters was analyzed using the limma software package to assess the prognostic value of RORC. Timer2.0 and DriverDBv3 were used to analyze the RORC mutation and methylation profiles. RORC-associated signaling pathways were identified by GSEA. The correlations of RORC expression with tumor microenvironment factors were further assessed, including immune cell infiltration (obtained by CIBERSORT) and immunomodulators (in pancancer datasets from the Tumor-Immune System Interactions and Drug Bank [TISIDB] database). In addition, the correlations of RORC with four CIT biomarkers (tumor mutational burden, microsatellite instability, programmed death ligand-1, and mismatch repair) were explored. Furthermore, three CIT cohorts (GSE67501, GSE168204, and IMvigor210) from the Gene Expression Omnibus database and a previously published study were used to determine the association between RORC expression and CIT response. Results: RORC was differentially expressed in many tumor tissues relative to normal tissues (20/33). In a small number of cancers, RORC expression was correlated with age (7/33), sex (4/33), and tumor stage (9/33). Furthermore, RORC expression showed prognostic value in many cancers, especially in kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and mesothelioma (MESO). The mutation rate of RORC in most cancer types was low, while RORC was hypermethylated or hypomethylated in multiple cancers. RORC was associated with a variety of biological processes and signal transduction pathways in various cancers. Furthermore, RORC was strongly correlated with immune cell infiltration, immunomodulators, and CIT biomarkers. However, no significant association was found between RORC and CIT response in the three CIT cohorts. Conclusion Our findings revealed the potential immunotherapeutic value of RORC for various cancers and provides preliminary evidence for the application of RORC in CIT. |
format | Online Article Text |
id | pubmed-9520743 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95207432022-09-30 A comprehensive pancancer analysis reveals the potential value of RAR-related orphan receptor C (RORC) for cancer immunotherapy He, Shengfu Yu, Jiawen Sun, Weijie Sun, Yating Tang, Mingyang Meng, Bao Liu, Yanyan Li, Jiabin Front Genet Genetics Background: RAR-related orphan receptor C (RORC) plays an important role in autoimmune responses and inflammation. However, its function in cancer immunity is still unclear. Its potential value in cancer immunotherapy (CIT) needs to be further studied. Methods: Expression and clinical data for 33 cancers were obtained from UCSC-Xena. The correlation between RORC expression and clinical parameters was analyzed using the limma software package to assess the prognostic value of RORC. Timer2.0 and DriverDBv3 were used to analyze the RORC mutation and methylation profiles. RORC-associated signaling pathways were identified by GSEA. The correlations of RORC expression with tumor microenvironment factors were further assessed, including immune cell infiltration (obtained by CIBERSORT) and immunomodulators (in pancancer datasets from the Tumor-Immune System Interactions and Drug Bank [TISIDB] database). In addition, the correlations of RORC with four CIT biomarkers (tumor mutational burden, microsatellite instability, programmed death ligand-1, and mismatch repair) were explored. Furthermore, three CIT cohorts (GSE67501, GSE168204, and IMvigor210) from the Gene Expression Omnibus database and a previously published study were used to determine the association between RORC expression and CIT response. Results: RORC was differentially expressed in many tumor tissues relative to normal tissues (20/33). In a small number of cancers, RORC expression was correlated with age (7/33), sex (4/33), and tumor stage (9/33). Furthermore, RORC expression showed prognostic value in many cancers, especially in kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and mesothelioma (MESO). The mutation rate of RORC in most cancer types was low, while RORC was hypermethylated or hypomethylated in multiple cancers. RORC was associated with a variety of biological processes and signal transduction pathways in various cancers. Furthermore, RORC was strongly correlated with immune cell infiltration, immunomodulators, and CIT biomarkers. However, no significant association was found between RORC and CIT response in the three CIT cohorts. Conclusion Our findings revealed the potential immunotherapeutic value of RORC for various cancers and provides preliminary evidence for the application of RORC in CIT. Frontiers Media S.A. 2022-09-15 /pmc/articles/PMC9520743/ /pubmed/36186454 http://dx.doi.org/10.3389/fgene.2022.969476 Text en Copyright © 2022 He, Yu, Sun, Sun, Tang, Meng, Liu and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics He, Shengfu Yu, Jiawen Sun, Weijie Sun, Yating Tang, Mingyang Meng, Bao Liu, Yanyan Li, Jiabin A comprehensive pancancer analysis reveals the potential value of RAR-related orphan receptor C (RORC) for cancer immunotherapy |
title | A comprehensive pancancer analysis reveals the potential value of RAR-related orphan receptor C (RORC) for cancer immunotherapy |
title_full | A comprehensive pancancer analysis reveals the potential value of RAR-related orphan receptor C (RORC) for cancer immunotherapy |
title_fullStr | A comprehensive pancancer analysis reveals the potential value of RAR-related orphan receptor C (RORC) for cancer immunotherapy |
title_full_unstemmed | A comprehensive pancancer analysis reveals the potential value of RAR-related orphan receptor C (RORC) for cancer immunotherapy |
title_short | A comprehensive pancancer analysis reveals the potential value of RAR-related orphan receptor C (RORC) for cancer immunotherapy |
title_sort | comprehensive pancancer analysis reveals the potential value of rar-related orphan receptor c (rorc) for cancer immunotherapy |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520743/ https://www.ncbi.nlm.nih.gov/pubmed/36186454 http://dx.doi.org/10.3389/fgene.2022.969476 |
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