Identification of an m6A Regulators-Mediated Prognosis Signature For Survival Prediction and Its Relevance to Immune Infiltration in Melanoma

Despite robust evidence for the role of m6A in cancer development and progression, its association with immune infiltration and survival outcomes in melanoma remains obscure. Here, we aimed to develop an m6A-related risk signature to improve prognostic and immunotherapy responder prediction performa...

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Autores principales:	Liuxing Wu, Xin Hu, Hongji Dai, Kexin Chen, Ben Liu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	signature for prognosis guidance immune infiltration melanoma m6A clusters expression pattern of m6A regulators Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/615e10dc7b3c44b4b8f20b31dc0e7f22
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spelling	oai:doaj.org-article:615e10dc7b3c44b4b8f20b31dc0e7f222021-12-01T01:37:25ZIdentification of an m6A Regulators-Mediated Prognosis Signature For Survival Prediction and Its Relevance to Immune Infiltration in Melanoma2296-634X10.3389/fcell.2021.718912https://doaj.org/article/615e10dc7b3c44b4b8f20b31dc0e7f222021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.718912/fullhttps://doaj.org/toc/2296-634XDespite robust evidence for the role of m6A in cancer development and progression, its association with immune infiltration and survival outcomes in melanoma remains obscure. Here, we aimed to develop an m6A-related risk signature to improve prognostic and immunotherapy responder prediction performance in the context of melanoma. We comprehensively analyzed the m6A cluster and immune infiltration phenotypes of public datasets. The TCGA (n = 457) and eleven independent melanoma cohorts (n = 758) were used as the training and validation datasets, respectively. We identified two m6A clusters (m6A-clusterA and m6A-clusterB) based on the expression pattern of m6A regulators via unsupervised consensus clustering. IGF2BP1 (7.49%), KIAA1429 (7.06%), and YTHDC1 (4.28%) were the three most frequently mutated genes. There was a correlation between driver genes mutation statuses and the expression of m6A regulators. A significant difference in tumor-associated immune infiltration between two m6A clusters was detected. Compared with m6A-clusterA, the m6A-clusterB was characterized by a lower immune score and immune cell infiltration but higher mRNA expression-based stemness index (mRNAsi). An m6A-related risk signature consisting of 12 genes was determined via Cox regression analysis and divided the patients into low- and high-risk groups (IL6ST, MBNL1, NXT2, EIF2A, CSGALNACT1, C11orf58, CD14, SPI1, NCCRP1, BOK, CD74, PAEP). A nomogram was developed for the prediction of the survival rate. Compared with the high-risk group, the low-risk group was characterized by high expression of immune checkpoints and immunophenoscore (IPS), activation of immune-related pathways, and more enriched in immune cell infiltrations. The low-risk group had a favorable prognosis and contained the potential beneficiaries of the immune checkpoint blockade therapy and verified by the IMvigor210 cohort (n = 298). The m6A-related signature we have determined in melanoma highlights the relationships between m6A regulators and immune cell infiltration. The established risk signature was identified as a promising clinical biomarker of melanoma.Liuxing WuXin HuHongji DaiKexin ChenBen LiuFrontiers Media S.A.articlesignature for prognosis guidanceimmune infiltrationmelanomam6A clustersexpression pattern of m6A regulatorsBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	signature for prognosis guidance immune infiltration melanoma m6A clusters expression pattern of m6A regulators Biology (General) QH301-705.5
spellingShingle	signature for prognosis guidance immune infiltration melanoma m6A clusters expression pattern of m6A regulators Biology (General) QH301-705.5 Liuxing Wu Xin Hu Hongji Dai Kexin Chen Ben Liu Identification of an m6A Regulators-Mediated Prognosis Signature For Survival Prediction and Its Relevance to Immune Infiltration in Melanoma
description	Despite robust evidence for the role of m6A in cancer development and progression, its association with immune infiltration and survival outcomes in melanoma remains obscure. Here, we aimed to develop an m6A-related risk signature to improve prognostic and immunotherapy responder prediction performance in the context of melanoma. We comprehensively analyzed the m6A cluster and immune infiltration phenotypes of public datasets. The TCGA (n = 457) and eleven independent melanoma cohorts (n = 758) were used as the training and validation datasets, respectively. We identified two m6A clusters (m6A-clusterA and m6A-clusterB) based on the expression pattern of m6A regulators via unsupervised consensus clustering. IGF2BP1 (7.49%), KIAA1429 (7.06%), and YTHDC1 (4.28%) were the three most frequently mutated genes. There was a correlation between driver genes mutation statuses and the expression of m6A regulators. A significant difference in tumor-associated immune infiltration between two m6A clusters was detected. Compared with m6A-clusterA, the m6A-clusterB was characterized by a lower immune score and immune cell infiltration but higher mRNA expression-based stemness index (mRNAsi). An m6A-related risk signature consisting of 12 genes was determined via Cox regression analysis and divided the patients into low- and high-risk groups (IL6ST, MBNL1, NXT2, EIF2A, CSGALNACT1, C11orf58, CD14, SPI1, NCCRP1, BOK, CD74, PAEP). A nomogram was developed for the prediction of the survival rate. Compared with the high-risk group, the low-risk group was characterized by high expression of immune checkpoints and immunophenoscore (IPS), activation of immune-related pathways, and more enriched in immune cell infiltrations. The low-risk group had a favorable prognosis and contained the potential beneficiaries of the immune checkpoint blockade therapy and verified by the IMvigor210 cohort (n = 298). The m6A-related signature we have determined in melanoma highlights the relationships between m6A regulators and immune cell infiltration. The established risk signature was identified as a promising clinical biomarker of melanoma.
format	article
author	Liuxing Wu Xin Hu Hongji Dai Kexin Chen Ben Liu
author_facet	Liuxing Wu Xin Hu Hongji Dai Kexin Chen Ben Liu
author_sort	Liuxing Wu
title	Identification of an m6A Regulators-Mediated Prognosis Signature For Survival Prediction and Its Relevance to Immune Infiltration in Melanoma
title_short	Identification of an m6A Regulators-Mediated Prognosis Signature For Survival Prediction and Its Relevance to Immune Infiltration in Melanoma
title_full	Identification of an m6A Regulators-Mediated Prognosis Signature For Survival Prediction and Its Relevance to Immune Infiltration in Melanoma
title_fullStr	Identification of an m6A Regulators-Mediated Prognosis Signature For Survival Prediction and Its Relevance to Immune Infiltration in Melanoma
title_full_unstemmed	Identification of an m6A Regulators-Mediated Prognosis Signature For Survival Prediction and Its Relevance to Immune Infiltration in Melanoma
title_sort	identification of an m6a regulators-mediated prognosis signature for survival prediction and its relevance to immune infiltration in melanoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/615e10dc7b3c44b4b8f20b31dc0e7f22
work_keys_str_mv	AT liuxingwu identificationofanm6aregulatorsmediatedprognosissignatureforsurvivalpredictionanditsrelevancetoimmuneinfiltrationinmelanoma AT xinhu identificationofanm6aregulatorsmediatedprognosissignatureforsurvivalpredictionanditsrelevancetoimmuneinfiltrationinmelanoma AT hongjidai identificationofanm6aregulatorsmediatedprognosissignatureforsurvivalpredictionanditsrelevancetoimmuneinfiltrationinmelanoma AT kexinchen identificationofanm6aregulatorsmediatedprognosissignatureforsurvivalpredictionanditsrelevancetoimmuneinfiltrationinmelanoma AT benliu identificationofanm6aregulatorsmediatedprognosissignatureforsurvivalpredictionanditsrelevancetoimmuneinfiltrationinmelanoma
_version_	1718405962117677056

Identification of an m6A Regulators-Mediated Prognosis Signature For Survival Prediction and Its Relevance to Immune Infiltration in Melanoma

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