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Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades

The common gamma receptor–dependent cytokines and their JAK-STAT pathways play important roles in T cell immunity and have been demonstrated to be related with response to immune checkpoint blockades (ICBs). PTPRD and PTPRT are phosphatases involved in JAK-STAT pathway. However, their clinical signi...

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Autores principales: Wang, Xiaoyan, Wu, Bingchen, Yan, Zhengqing, Wang, Guoqiang, Chen, Shiqing, Zeng, Jian, Tao, Feng, Xu, Bichun, Ke, Honggang, Li, Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192300/
https://www.ncbi.nlm.nih.gov/pubmed/34123798
http://dx.doi.org/10.3389/fonc.2021.650122
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author Wang, Xiaoyan
Wu, Bingchen
Yan, Zhengqing
Wang, Guoqiang
Chen, Shiqing
Zeng, Jian
Tao, Feng
Xu, Bichun
Ke, Honggang
Li, Mei
author_facet Wang, Xiaoyan
Wu, Bingchen
Yan, Zhengqing
Wang, Guoqiang
Chen, Shiqing
Zeng, Jian
Tao, Feng
Xu, Bichun
Ke, Honggang
Li, Mei
author_sort Wang, Xiaoyan
collection PubMed
description The common gamma receptor–dependent cytokines and their JAK-STAT pathways play important roles in T cell immunity and have been demonstrated to be related with response to immune checkpoint blockades (ICBs). PTPRD and PTPRT are phosphatases involved in JAK-STAT pathway. However, their clinical significance for non-small cell lung cancer (NSCLC) treated with ICBs is still unclear. Genomic and survival data of NSCLC patients administrated with anti–PD-1/PD-L1 or anti–CTLA-4 antibodies (Rizvi2015; Hellmann2018; Rizvi2018 Samstein2019) were retrieved from publicly accessible data. Genomic, survival and mRNA data of 1007 patients with NSCLC were obtained from The Cancer Genome Atlas (TCGA). PTPRD/PTPRT mutation was significantly associated with better progression-free survival (PFS) in three independent Rizvi2015, Hellmann2018 and Rizvi2018 cohorts. The median PFS for PTPRD/PTPRT mutant-type vs. wild-type NSCLC patients were not reached vs. 6.3 months (Rizvi2015, HR = 0.16; 95% CI, 0.02-1.17; P=0.03), 24.0 vs. 5.4 months (Hellmann2018, HR, 0.49; 95% CI, 0.26-0.94; P=0.03), 5.6 vs. 3.0 months (Rizvi2018, HR = 0.64; 95% CI, 0.44-0.92; P=0.01) and 6.8 vs. 3.5 months (Pooled cohort, HR, 0.54; 95% CI, 0.39-0.73; P<0.0001) respectively. PTPRD/PTPRT mutation was an independent predictive factor for PFS in pooled cohort (P = 0.01). Additionally, PTPRD/PTPRT mutation associated with better overall survival (OS) in Samstein2019 cohort (19 vs. 10 months, P=0.03). While similar clinical benefits were not observed in patients without ICBs treatment (TCGA cohort, P=0.78). In the further exploratory analysis, PTPRD/PTPRT mutation was significantly associated with increased tumor mutation burden and higher mRNA expression of JAK1 and STAT1. Gene Set Enrichment Analysis revealed prominent enrichment of signatures related to antigen processing and presentation in patients with PTPRD/PTPRT mutation. This work suggested that PTPRD/PTPRT mutation might be a potential positive predictor for ICBs in NSCLC. These results need to be further confirmed in future.
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spelling pubmed-81923002021-06-12 Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades Wang, Xiaoyan Wu, Bingchen Yan, Zhengqing Wang, Guoqiang Chen, Shiqing Zeng, Jian Tao, Feng Xu, Bichun Ke, Honggang Li, Mei Front Oncol Oncology The common gamma receptor–dependent cytokines and their JAK-STAT pathways play important roles in T cell immunity and have been demonstrated to be related with response to immune checkpoint blockades (ICBs). PTPRD and PTPRT are phosphatases involved in JAK-STAT pathway. However, their clinical significance for non-small cell lung cancer (NSCLC) treated with ICBs is still unclear. Genomic and survival data of NSCLC patients administrated with anti–PD-1/PD-L1 or anti–CTLA-4 antibodies (Rizvi2015; Hellmann2018; Rizvi2018 Samstein2019) were retrieved from publicly accessible data. Genomic, survival and mRNA data of 1007 patients with NSCLC were obtained from The Cancer Genome Atlas (TCGA). PTPRD/PTPRT mutation was significantly associated with better progression-free survival (PFS) in three independent Rizvi2015, Hellmann2018 and Rizvi2018 cohorts. The median PFS for PTPRD/PTPRT mutant-type vs. wild-type NSCLC patients were not reached vs. 6.3 months (Rizvi2015, HR = 0.16; 95% CI, 0.02-1.17; P=0.03), 24.0 vs. 5.4 months (Hellmann2018, HR, 0.49; 95% CI, 0.26-0.94; P=0.03), 5.6 vs. 3.0 months (Rizvi2018, HR = 0.64; 95% CI, 0.44-0.92; P=0.01) and 6.8 vs. 3.5 months (Pooled cohort, HR, 0.54; 95% CI, 0.39-0.73; P<0.0001) respectively. PTPRD/PTPRT mutation was an independent predictive factor for PFS in pooled cohort (P = 0.01). Additionally, PTPRD/PTPRT mutation associated with better overall survival (OS) in Samstein2019 cohort (19 vs. 10 months, P=0.03). While similar clinical benefits were not observed in patients without ICBs treatment (TCGA cohort, P=0.78). In the further exploratory analysis, PTPRD/PTPRT mutation was significantly associated with increased tumor mutation burden and higher mRNA expression of JAK1 and STAT1. Gene Set Enrichment Analysis revealed prominent enrichment of signatures related to antigen processing and presentation in patients with PTPRD/PTPRT mutation. This work suggested that PTPRD/PTPRT mutation might be a potential positive predictor for ICBs in NSCLC. These results need to be further confirmed in future. Frontiers Media S.A. 2021-05-27 /pmc/articles/PMC8192300/ /pubmed/34123798 http://dx.doi.org/10.3389/fonc.2021.650122 Text en Copyright © 2021 Wang, Wu, Yan, Wang, Chen, Zeng, Tao, Xu, Ke and Li 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 Oncology
Wang, Xiaoyan
Wu, Bingchen
Yan, Zhengqing
Wang, Guoqiang
Chen, Shiqing
Zeng, Jian
Tao, Feng
Xu, Bichun
Ke, Honggang
Li, Mei
Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades
title Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades
title_full Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades
title_fullStr Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades
title_full_unstemmed Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades
title_short Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades
title_sort association of ptprd/ptprt mutation with better clinical outcomes in nsclc patients treated with immune checkpoint blockades
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192300/
https://www.ncbi.nlm.nih.gov/pubmed/34123798
http://dx.doi.org/10.3389/fonc.2021.650122
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