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A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma
Background: Melanoma is the most lethal, and one of the most aggressive forms of cutaneous malignancies, which poor response to treatment has always puzzled clinicians. As is known to all, aging and immune microenvironment are two crucial factors impacting melanoma biological progress through the tu...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9402914/ https://www.ncbi.nlm.nih.gov/pubmed/36034849 http://dx.doi.org/10.3389/fphar.2022.943944 |
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author | Lv, Wenchang Zhan, YuanYuan Tan, Yufang Wu, Yiping Chen, Hongbo |
author_facet | Lv, Wenchang Zhan, YuanYuan Tan, Yufang Wu, Yiping Chen, Hongbo |
author_sort | Lv, Wenchang |
collection | PubMed |
description | Background: Melanoma is the most lethal, and one of the most aggressive forms of cutaneous malignancies, which poor response to treatment has always puzzled clinicians. As is known to all, aging and immune microenvironment are two crucial factors impacting melanoma biological progress through the tumor microenvironment (TME). However, reliable biomarkers for predicting melanoma prognosis based on aging and immune microenvironment and therapeutic efficacy of immune checkpoints remain to be determined. Methods: The aging-related genes (ARGs) were obtained from the Human Ageing Genomic Resources and immune-related genes (IRGs) were downloaded from the Immunology database as well as Analysis Portal (ImmPort) database. Next, we initially performed LASSO regression and multivariate Cox regression to identify prognostic ARGs and IRGs in the TCGA and GSE65904 datasets, and firstly constructed a novel comprehensive index of aging and immune (CIAI) signature. Finally, in vitro molecular biology experiments were performed to assess the regulatory role of CNTFR in melanoma cell lines proliferation and migration, macrophage recruitment, and M2 polarization. Results: This novel CIAI signature consisted of 7 genes, including FOXM1, TP63, ARNTL, KIR2DL4, CCL8, SEMA6A, and CNTFR, in which melanoma patients in the high-CIAI group had shorter OS, DSS, and PFI, indicating CIAI model served as an independent prognostic index. Moreover, we found the CIAI score was potentially correlated with immune scores, estimate score, immune cell infiltration level, tumor microenvironment, immunotherapy effect, and drug sensitivity. Finally, CNTFR might function as oncogenes in melanoma cell lines and the silencing of CNTFR reduced macrophage recruitment and M2 polarization. Conclusion: In this study, we have first presented a novel prognostic CIAI model applied to assess immune checkpoint therapy and the efficacy of conventional chemotherapy agents in melanoma patients. Thus providing a new insight for combating melanoma. |
format | Online Article Text |
id | pubmed-9402914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94029142022-08-26 A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma Lv, Wenchang Zhan, YuanYuan Tan, Yufang Wu, Yiping Chen, Hongbo Front Pharmacol Pharmacology Background: Melanoma is the most lethal, and one of the most aggressive forms of cutaneous malignancies, which poor response to treatment has always puzzled clinicians. As is known to all, aging and immune microenvironment are two crucial factors impacting melanoma biological progress through the tumor microenvironment (TME). However, reliable biomarkers for predicting melanoma prognosis based on aging and immune microenvironment and therapeutic efficacy of immune checkpoints remain to be determined. Methods: The aging-related genes (ARGs) were obtained from the Human Ageing Genomic Resources and immune-related genes (IRGs) were downloaded from the Immunology database as well as Analysis Portal (ImmPort) database. Next, we initially performed LASSO regression and multivariate Cox regression to identify prognostic ARGs and IRGs in the TCGA and GSE65904 datasets, and firstly constructed a novel comprehensive index of aging and immune (CIAI) signature. Finally, in vitro molecular biology experiments were performed to assess the regulatory role of CNTFR in melanoma cell lines proliferation and migration, macrophage recruitment, and M2 polarization. Results: This novel CIAI signature consisted of 7 genes, including FOXM1, TP63, ARNTL, KIR2DL4, CCL8, SEMA6A, and CNTFR, in which melanoma patients in the high-CIAI group had shorter OS, DSS, and PFI, indicating CIAI model served as an independent prognostic index. Moreover, we found the CIAI score was potentially correlated with immune scores, estimate score, immune cell infiltration level, tumor microenvironment, immunotherapy effect, and drug sensitivity. Finally, CNTFR might function as oncogenes in melanoma cell lines and the silencing of CNTFR reduced macrophage recruitment and M2 polarization. Conclusion: In this study, we have first presented a novel prognostic CIAI model applied to assess immune checkpoint therapy and the efficacy of conventional chemotherapy agents in melanoma patients. Thus providing a new insight for combating melanoma. Frontiers Media S.A. 2022-08-11 /pmc/articles/PMC9402914/ /pubmed/36034849 http://dx.doi.org/10.3389/fphar.2022.943944 Text en Copyright © 2022 Lv, Zhan, Tan, Wu and Chen. 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 | Pharmacology Lv, Wenchang Zhan, YuanYuan Tan, Yufang Wu, Yiping Chen, Hongbo A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma |
title | A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma |
title_full | A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma |
title_fullStr | A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma |
title_full_unstemmed | A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma |
title_short | A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma |
title_sort | combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9402914/ https://www.ncbi.nlm.nih.gov/pubmed/36034849 http://dx.doi.org/10.3389/fphar.2022.943944 |
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