Frontiers in Immunology (Oct 2022)
Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma
- Fang Wang,
- Fang Wang,
- Anfu Zheng,
- Duoli Zhang,
- Tao Zou,
- Mintao Xiao,
- Jie Chen,
- Bo Wen,
- Qinglian Wen,
- Xu Wu,
- Xu Wu,
- Xu Wu,
- Mingxing Li,
- Mingxing Li,
- Mingxing Li,
- Fukuan Du,
- Fukuan Du,
- Fukuan Du,
- Yu Chen,
- Yu Chen,
- Yu Chen,
- Yueshui Zhao,
- Yueshui Zhao,
- Yueshui Zhao,
- Jing Shen,
- Jing Shen,
- Jing Shen,
- Shixin Xiang,
- Jing Li,
- Shuai Deng,
- Shuai Deng,
- Shuai Deng,
- Zhuo Zhang,
- Zhuo Zhang,
- Tao Yi,
- Zhangang Xiao,
- Zhangang Xiao,
- Zhangang Xiao
Affiliations
- Fang Wang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Fang Wang
- Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
- Anfu Zheng
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Duoli Zhang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Tao Zou
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Mintao Xiao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Jie Chen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Bo Wen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Qinglian Wen
- Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Xu Wu
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Xu Wu
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- Xu Wu
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
- Mingxing Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Mingxing Li
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- Mingxing Li
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
- Fukuan Du
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Fukuan Du
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- Fukuan Du
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
- Yu Chen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Yu Chen
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- Yu Chen
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
- Yueshui Zhao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Yueshui Zhao
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- Yueshui Zhao
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
- Jing Shen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Jing Shen
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- Jing Shen
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
- Shixin Xiang
- Department of Pharmacy, University-Town Hospital of Chongqing Medical University, Chongqing, China
- Jing Li
- Department of Oncology and Hematology, The Affiliated Traditional Chinese Medicine (TCM) Hospital of Southwest Medical University, Luzhou, China
- Shuai Deng
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Shuai Deng
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- Shuai Deng
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
- Zhuo Zhang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Zhuo Zhang
- Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
- Tao Yi
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Hong Kong SAR, China
- Zhangang Xiao
- Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- Zhangang Xiao
- Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- Zhangang Xiao
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
- DOI
- https://doi.org/10.3389/fimmu.2022.1024931
- Journal volume & issue
-
Vol. 13
Abstract
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.
Keywords
