Molecular profiling of core immune-escape genes highlights LCK as an immune-related prognostic biomarker in melanoma

作者全名："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"

作者地址："[Wang, Fang; Zheng, Anfu; Zhang, Duoli; Zou, Tao; Xiao, Mintao; Chen, Jie; Wen, Bo; Wu, Xu; Li, Mingxing; Du, Fukuan; Chen, Yu; Zhao, Yueshui; Shen, Jing; Deng, Shuai; Zhang, Zhuo] Southwest Med Univ, Sch Pharm, Dept Pharmacol, Lab Mol Pharmacol, Luzhou, Peoples R China; [Wang, Fang; Zhang, Zhuo] Chiang Mai Univ, Fac Associated Med Sci, Dept Med Technol, Chiang Mai, Thailand; [Wen, Qinglian; Xiao, Zhangang] Southwest Med Univ, Dept Oncol, Affiliated Hosp, Luzhou, Sichuan, Peoples R China; [Wu, Xu; Li, Mingxing; Du, Fukuan; Chen, Yu; Zhao, Yueshui; Shen, Jing; Deng, Shuai; Xiao, Zhangang] Cell Therapy & Cell Drugs Luzhou Key Lab, Luzhou, Sichuan, Peoples R China; [Wu, Xu; Li, Mingxing; Du, Fukuan; Chen, Yu; Zhao, Yueshui; Shen, Jing; Deng, Shuai; Xiao, Zhangang] South Sichuan Inst Translat Med, Luzhou, Sichuan, Peoples R China; [Xiang, Shixin] Chongqing Med Univ, Univ Town Hosp, Dept Pharm, Chongqing, Peoples R China; [Li, Jing] Southwest Med Univ, Dept Oncol & Hematol, Affiliated Tradit Chinese Med TCM Hosp, Luzhou, Peoples R China; [Yi, Tao] Hong Kong Baptist Univ, Sch Chinese Med, Hong Kong, Peoples R China"

通信作者："Zhang, Z (通讯作者)，Southwest Med Univ, Sch Pharm, Dept Pharmacol, Lab Mol Pharmacol, Luzhou, Peoples R China.; Zhang, Z (通讯作者)，Chiang Mai Univ, Fac Associated Med Sci, Dept Med Technol, Chiang Mai, Thailand.; Xiao, ZA (通讯作者)，Southwest Med Univ, Dept Oncol, Affiliated Hosp, Luzhou, Sichuan, Peoples R China.; Xiao, ZA (通讯作者)，Cell Therapy & Cell Drugs Luzhou Key Lab, Luzhou, Sichuan, Peoples R China.; Xiao, ZA (通讯作者)，South Sichuan Inst Translat Med, Luzhou, Sichuan, Peoples R China.; Yi, T (通讯作者)，Hong Kong Baptist Univ, Sch Chinese Med, Hong Kong, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000890478500001

JCR分区：Q1

影响因子：7.3

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：melanoma; single-cell sequence; tme; oncoPredict; immune escape

摘要："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."

基金机构："National Natural Science Foundation of China [81972643, 82172962]; Sichuan Science and Technology Project [2021YJ0201]; Luxian People's Government; Southwest Medical University Scientific and Technological Achievements Transfer and Transformation Strategic Cooperation Project [2019LXXNYKD-07]; Science and Technology Program of Luzhou, China [2017LZXNYD-Z04, 21CGZHPT0001]"

基金资助正文："This work was supported by National Natural Science Foundation of China (No. 81972643, No. 82172962), Sichuan Science and Technology Project (2021YJ0201), Luxian People's Government and Southwest Medical University Scientific and Technological Achievements Transfer and Transformation Strategic Cooperation Project (2019LXXNYKD-07) and Science and Technology Program of Luzhou, China (No. 2017LZXNYD-Z04, No. 21CGZHPT0001)."