Pan-Cancer Analysis Reveals the Signature of TMC Family of Genes as a Promising Biomarker for Prognosis and Immunotherapeutic Response

Transmembrane Channel-like (TMC) genes are critical in the carcinogenesis, proliferation, and cell cycle of human cancers. However, the multi-omics features of TMCs and their role in the prognosis and immunotherapeutic response of human cancer have not been explored. We discovered that TMCs 4-8 were...

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Autores principales:	Jing Song, Yongyao Tang, Xiaoyong Luo, Xinpeng Shi, Fangzhou Song, Longke Ran
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	transmembrane channel-like proteins multi-omics pan-cancer analysis biomarker immune-infiltrating immunotherapy Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/250e2cd9f4164b6b87e7284a1e755993
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spelling	oai:doaj.org-article:250e2cd9f4164b6b87e7284a1e7559932021-11-09T06:12:50ZPan-Cancer Analysis Reveals the Signature of TMC Family of Genes as a Promising Biomarker for Prognosis and Immunotherapeutic Response1664-322410.3389/fimmu.2021.715508https://doaj.org/article/250e2cd9f4164b6b87e7284a1e7559932021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.715508/fullhttps://doaj.org/toc/1664-3224Transmembrane Channel-like (TMC) genes are critical in the carcinogenesis, proliferation, and cell cycle of human cancers. However, the multi-omics features of TMCs and their role in the prognosis and immunotherapeutic response of human cancer have not been explored. We discovered that TMCs 4-8 were commonly deregulated and correlated with patient survival in a variety of cancers. For example, TMC5 and TMC8 were correlated with the relapse and overall survival rates of breast cancer and skin melanoma, respectively. These results were validated by multiple independent cohorts. TMCs were regulated by DNA methylation and somatic alterations, such as TMC5 amplification in breast cancer (523/1062, 49.2%). Six algorithms concordantly uncovered the critical role of TMCs in the tumor microenvironment, potentially regulating immune cell toxicity and lymphocytes infiltration. Moreover, TMCs 4-8 were correlated with tumor mutation burden and expression of PD-1/PD-L1/CTLA4 in 33 cancers. Thus, we established an immunotherapy response prediction (IRP) score based on the signature of TMCs 4-8. Patients with higher IRP scores showed higher immunotherapeutic responses in five cohorts of skin melanoma (area under curve [AUC] = 0.90 in the training cohort, AUCs range from 0.70 to 0.83 in the validation cohorts). Together, our study highlights the great potential of TMCs as biomarkers for prognosis and immunotherapeutic response, which can pave the way for further investigation of the tumor-infiltrating mechanisms and therapeutic potentials of TMCs in cancer.Jing SongJing SongYongyao TangXiaoyong LuoXinpeng ShiFangzhou SongLongke RanLongke RanFrontiers Media S.A.articletransmembrane channel-like proteinsmulti-omicspan-cancer analysisbiomarkerimmune-infiltratingimmunotherapyImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	transmembrane channel-like proteins multi-omics pan-cancer analysis biomarker immune-infiltrating immunotherapy Immunologic diseases. Allergy RC581-607
spellingShingle	transmembrane channel-like proteins multi-omics pan-cancer analysis biomarker immune-infiltrating immunotherapy Immunologic diseases. Allergy RC581-607 Jing Song Jing Song Yongyao Tang Xiaoyong Luo Xinpeng Shi Fangzhou Song Longke Ran Longke Ran Pan-Cancer Analysis Reveals the Signature of TMC Family of Genes as a Promising Biomarker for Prognosis and Immunotherapeutic Response
description	Transmembrane Channel-like (TMC) genes are critical in the carcinogenesis, proliferation, and cell cycle of human cancers. However, the multi-omics features of TMCs and their role in the prognosis and immunotherapeutic response of human cancer have not been explored. We discovered that TMCs 4-8 were commonly deregulated and correlated with patient survival in a variety of cancers. For example, TMC5 and TMC8 were correlated with the relapse and overall survival rates of breast cancer and skin melanoma, respectively. These results were validated by multiple independent cohorts. TMCs were regulated by DNA methylation and somatic alterations, such as TMC5 amplification in breast cancer (523/1062, 49.2%). Six algorithms concordantly uncovered the critical role of TMCs in the tumor microenvironment, potentially regulating immune cell toxicity and lymphocytes infiltration. Moreover, TMCs 4-8 were correlated with tumor mutation burden and expression of PD-1/PD-L1/CTLA4 in 33 cancers. Thus, we established an immunotherapy response prediction (IRP) score based on the signature of TMCs 4-8. Patients with higher IRP scores showed higher immunotherapeutic responses in five cohorts of skin melanoma (area under curve [AUC] = 0.90 in the training cohort, AUCs range from 0.70 to 0.83 in the validation cohorts). Together, our study highlights the great potential of TMCs as biomarkers for prognosis and immunotherapeutic response, which can pave the way for further investigation of the tumor-infiltrating mechanisms and therapeutic potentials of TMCs in cancer.
format	article
author	Jing Song Jing Song Yongyao Tang Xiaoyong Luo Xinpeng Shi Fangzhou Song Longke Ran Longke Ran
author_facet	Jing Song Jing Song Yongyao Tang Xiaoyong Luo Xinpeng Shi Fangzhou Song Longke Ran Longke Ran
author_sort	Jing Song
title	Pan-Cancer Analysis Reveals the Signature of TMC Family of Genes as a Promising Biomarker for Prognosis and Immunotherapeutic Response
title_short	Pan-Cancer Analysis Reveals the Signature of TMC Family of Genes as a Promising Biomarker for Prognosis and Immunotherapeutic Response
title_full	Pan-Cancer Analysis Reveals the Signature of TMC Family of Genes as a Promising Biomarker for Prognosis and Immunotherapeutic Response
title_fullStr	Pan-Cancer Analysis Reveals the Signature of TMC Family of Genes as a Promising Biomarker for Prognosis and Immunotherapeutic Response
title_full_unstemmed	Pan-Cancer Analysis Reveals the Signature of TMC Family of Genes as a Promising Biomarker for Prognosis and Immunotherapeutic Response
title_sort	pan-cancer analysis reveals the signature of tmc family of genes as a promising biomarker for prognosis and immunotherapeutic response
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/250e2cd9f4164b6b87e7284a1e755993
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Pan-Cancer Analysis Reveals the Signature of TMC Family of Genes as a Promising Biomarker for Prognosis and Immunotherapeutic Response

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