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Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma
The tumor microenvironment is complicated and continuously evolving. This study was devoted to the identification of potential prognostic biomarkers based on the tumor microenvironment associated with immunotherapy for melanoma. This study integrates a couple of melanoma single cell and transcriptom...
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/PMC9630653/ https://www.ncbi.nlm.nih.gov/pubmed/36341345 http://dx.doi.org/10.3389/fimmu.2022.1024931 |
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author | Wang, Fang Zheng, Anfu Zhang, Duoli Zou, Tao Xiao, Mintao Chen, Jie Wen, Bo Wen, Qinglian Wu, Xu Li, Mingxing Du, Fukuan Chen, Yu Zhao, Yueshui Shen, Jing Xiang, Shixin Li, Jing Deng, Shuai Zhang, Zhuo Yi, Tao Xiao, Zhangang |
author_facet | Wang, Fang Zheng, Anfu Zhang, Duoli Zou, Tao Xiao, Mintao Chen, Jie Wen, Bo Wen, Qinglian Wu, Xu Li, Mingxing Du, Fukuan Chen, Yu Zhao, Yueshui Shen, Jing Xiang, Shixin Li, Jing Deng, Shuai Zhang, Zhuo Yi, Tao Xiao, Zhangang |
author_sort | Wang, Fang |
collection | PubMed |
description | The tumor microenvironment is complicated and continuously evolving. This study was devoted to the identification of potential prognostic biomarkers based on the tumor microenvironment associated with immunotherapy for melanoma. This study integrates a couple of melanoma single cell and transcriptome sequencing datasets and performs a series of silico analyses as nicely as validation of molecular biology techniques. A core set of immune escape related genes was identified through Lawson et al. and the ImmPort portal. The differential proteins were identified through the cBioPortal database. Regression analysis was used to profile independent prognostic factors. Correlation with the level of immune cell infiltration was evaluated by multiple algorithms. The capacity of LCK to predict response was assessed in two independent immunotherapy cohorts. High LCK expression is associated with better prognosis, high levels of TILs and better clinical staging. Pathway analysis showed that high expression of LCK was significantly associated with activation of multiple tumor pathways as well as immune-related pathways. LCK expression tends to be higher in immunotherapy-responsive patients and those with lower IC50s treated with chemotherapeutic agents. RT-qPCR detected that LCK expression was significantly upregulated in melanoma cell lines. Single-cell transcriptome analysis showed that LCK was specifically highly expressed on T cells. CellChat analysis confirmed that LCK in C2 subpopulations and T cell subpopulations exerted immune promotion between cells by binding to CD8 receptors. In conclusion, LCK is a reliable biomarker for melanoma and will contribute to its immunotherapy. |
format | Online Article Text |
id | pubmed-9630653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96306532022-11-04 Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma Wang, Fang Zheng, Anfu Zhang, Duoli Zou, Tao Xiao, Mintao Chen, Jie Wen, Bo Wen, Qinglian Wu, Xu Li, Mingxing Du, Fukuan Chen, Yu Zhao, Yueshui Shen, Jing Xiang, Shixin Li, Jing Deng, Shuai Zhang, Zhuo Yi, Tao Xiao, Zhangang Front Immunol Immunology The tumor microenvironment is complicated and continuously evolving. This study was devoted to the identification of potential prognostic biomarkers based on the tumor microenvironment associated with immunotherapy for melanoma. This study integrates a couple of melanoma single cell and transcriptome sequencing datasets and performs a series of silico analyses as nicely as validation of molecular biology techniques. A core set of immune escape related genes was identified through Lawson et al. and the ImmPort portal. The differential proteins were identified through the cBioPortal database. Regression analysis was used to profile independent prognostic factors. Correlation with the level of immune cell infiltration was evaluated by multiple algorithms. The capacity of LCK to predict response was assessed in two independent immunotherapy cohorts. High LCK expression is associated with better prognosis, high levels of TILs and better clinical staging. Pathway analysis showed that high expression of LCK was significantly associated with activation of multiple tumor pathways as well as immune-related pathways. LCK expression tends to be higher in immunotherapy-responsive patients and those with lower IC50s treated with chemotherapeutic agents. RT-qPCR detected that LCK expression was significantly upregulated in melanoma cell lines. Single-cell transcriptome analysis showed that LCK was specifically highly expressed on T cells. CellChat analysis confirmed that LCK in C2 subpopulations and T cell subpopulations exerted immune promotion between cells by binding to CD8 receptors. In conclusion, LCK is a reliable biomarker for melanoma and will contribute to its immunotherapy. Frontiers Media S.A. 2022-10-20 /pmc/articles/PMC9630653/ /pubmed/36341345 http://dx.doi.org/10.3389/fimmu.2022.1024931 Text en Copyright © 2022 Wang, Zheng, Zhang, Zou, Xiao, Chen, Wen, Wen, Wu, Li, Du, Chen, Zhao, Shen, Xiang, Li, Deng, Zhang, Yi and Xiao 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 | Immunology Wang, Fang Zheng, Anfu Zhang, Duoli Zou, Tao Xiao, Mintao Chen, Jie Wen, Bo Wen, Qinglian Wu, Xu Li, Mingxing Du, Fukuan Chen, Yu Zhao, Yueshui Shen, Jing Xiang, Shixin Li, Jing Deng, Shuai Zhang, Zhuo Yi, Tao Xiao, Zhangang Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma |
title | Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma |
title_full | Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma |
title_fullStr | Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma |
title_full_unstemmed | Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma |
title_short | Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma |
title_sort | molecular profiling of core immune-escape genes highlights lck as an immune-related prognostic biomarker in melanoma |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630653/ https://www.ncbi.nlm.nih.gov/pubmed/36341345 http://dx.doi.org/10.3389/fimmu.2022.1024931 |
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