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...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in oncology 2021-05, Vol.11, p.650122-650122
Main Authors: Wang, Xiaoyan, Wu, Bingchen, Yan, Zhengqing, Wang, Guoqiang, Chen, Shiqing, Zeng, Jian, Tao, Feng, Xu, Bichun, Ke, Honggang, Li, Mei
Format: Article
Language:English
Subjects:
immune checkpoint blockades
JAK-STAT
non-small cell lung cancer
Oncology
PTPRD
PTPRT
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c439t-60ced903a3199573cdb4fae1d28d37d8f0f59b6efb53fc0bcf2c40c2fe9fb56a3
cites cdi_FETCH-LOGICAL-c439t-60ced903a3199573cdb4fae1d28d37d8f0f59b6efb53fc0bcf2c40c2fe9fb56a3
container_end_page 650122
container_issue
container_start_page 650122
container_title Frontiers in oncology
container_volume 11
creator Wang, Xiaoyan
Wu, Bingchen
Yan, Zhengqing
Wang, Guoqiang
Chen, Shiqing
Zeng, Jian
Tao, Feng
Xu, Bichun
Ke, Honggang
Li, Mei
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
doi_str_mv 10.3389/fonc.2021.650122
format article
fullrecord <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_01b10a7acc604c4da996add6d718bf71</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_01b10a7acc604c4da996add6d718bf71</doaj_id><sourcerecordid>2540721436</sourcerecordid><originalsourceid>FETCH-LOGICAL-c439t-60ced903a3199573cdb4fae1d28d37d8f0f59b6efb53fc0bcf2c40c2fe9fb56a3</originalsourceid><addsrcrecordid>eNpVkstv1DAQxiMEolXpnaOPXHbrR16-ILXh0ZUWuoJFcLOc8bjrNokX20FC6h9PQipE5-AZff7mZ1n6suw1o2shanlh_QBrTjlblwVlnD_LTjkX-Urm4sfz_-aT7DzGOzrV7KPiZXYicsZFJevT7OEyRg9OJ-cH4i3Z7Xdf3l3M5558GtOif3fpQK4wJQyk6dzgQHfkZkzge4zEDeTz12bbkN3kxiFFsg-oE5plb9P344CkOSDcH70bErnqPNxrg_FV9sLqLuL5Yz_Lvn14v2-uV9ubj5vmcruCXMi0KimgkVRowaQsKgGmza1GZnhtRGVqS20h2xJtWwgLtAXLIafALcpJKrU4yzYL13h9p47B9Tr8Vl479Vfw4VbpkBx0qChrGdWVBihpDrnRUpbamNJUrG5txSbW24V1HNseDUwfDrp7An16M7iDuvW_VM0kF5ROgDePgOB_jhiT6l0E7Do9oB-j4kVOK85yUU5Wulgh-BgD2n_PMKrmDKg5A2rOgFoyIP4AAjql8g</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2540721436</pqid></control><display><type>article</type><title>Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades</title><source>PubMed (Medline)</source><creator>Wang, Xiaoyan ; Wu, Bingchen ; Yan, Zhengqing ; Wang, Guoqiang ; Chen, Shiqing ; Zeng, Jian ; Tao, Feng ; Xu, Bichun ; Ke, Honggang ; Li, Mei</creator><creatorcontrib>Wang, Xiaoyan ; Wu, Bingchen ; Yan, Zhengqing ; Wang, Guoqiang ; Chen, Shiqing ; Zeng, Jian ; Tao, Feng ; Xu, Bichun ; Ke, Honggang ; Li, Mei</creatorcontrib><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&lt;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.</description><identifier>ISSN: 2234-943X</identifier><identifier>EISSN: 2234-943X</identifier><identifier>DOI: 10.3389/fonc.2021.650122</identifier><identifier>PMID: 34123798</identifier><language>eng</language><publisher>Frontiers Media S.A</publisher><subject>immune checkpoint blockades ; JAK-STAT ; non-small cell lung cancer ; Oncology ; PTPRD ; PTPRT</subject><ispartof>Frontiers in oncology, 2021-05, Vol.11, p.650122-650122</ispartof><rights>Copyright © 2021 Wang, Wu, Yan, Wang, Chen, Zeng, Tao, Xu, Ke and Li 2021 Wang, Wu, Yan, Wang, Chen, Zeng, Tao, Xu, Ke and Li</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-60ced903a3199573cdb4fae1d28d37d8f0f59b6efb53fc0bcf2c40c2fe9fb56a3</citedby><cites>FETCH-LOGICAL-c439t-60ced903a3199573cdb4fae1d28d37d8f0f59b6efb53fc0bcf2c40c2fe9fb56a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192300/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192300/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids></links><search><creatorcontrib>Wang, Xiaoyan</creatorcontrib><creatorcontrib>Wu, Bingchen</creatorcontrib><creatorcontrib>Yan, Zhengqing</creatorcontrib><creatorcontrib>Wang, Guoqiang</creatorcontrib><creatorcontrib>Chen, Shiqing</creatorcontrib><creatorcontrib>Zeng, Jian</creatorcontrib><creatorcontrib>Tao, Feng</creatorcontrib><creatorcontrib>Xu, Bichun</creatorcontrib><creatorcontrib>Ke, Honggang</creatorcontrib><creatorcontrib>Li, Mei</creatorcontrib><title>Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades</title><title>Frontiers in oncology</title><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&lt;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.</description><subject>immune checkpoint blockades</subject><subject>JAK-STAT</subject><subject>non-small cell lung cancer</subject><subject>Oncology</subject><subject>PTPRD</subject><subject>PTPRT</subject><issn>2234-943X</issn><issn>2234-943X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVkstv1DAQxiMEolXpnaOPXHbrR16-ILXh0ZUWuoJFcLOc8bjrNokX20FC6h9PQipE5-AZff7mZ1n6suw1o2shanlh_QBrTjlblwVlnD_LTjkX-Urm4sfz_-aT7DzGOzrV7KPiZXYicsZFJevT7OEyRg9OJ-cH4i3Z7Xdf3l3M5558GtOif3fpQK4wJQyk6dzgQHfkZkzge4zEDeTz12bbkN3kxiFFsg-oE5plb9P344CkOSDcH70bErnqPNxrg_FV9sLqLuL5Yz_Lvn14v2-uV9ubj5vmcruCXMi0KimgkVRowaQsKgGmza1GZnhtRGVqS20h2xJtWwgLtAXLIafALcpJKrU4yzYL13h9p47B9Tr8Vl479Vfw4VbpkBx0qChrGdWVBihpDrnRUpbamNJUrG5txSbW24V1HNseDUwfDrp7An16M7iDuvW_VM0kF5ROgDePgOB_jhiT6l0E7Do9oB-j4kVOK85yUU5Wulgh-BgD2n_PMKrmDKg5A2rOgFoyIP4AAjql8g</recordid><startdate>20210527</startdate><enddate>20210527</enddate><creator>Wang, Xiaoyan</creator><creator>Wu, Bingchen</creator><creator>Yan, Zhengqing</creator><creator>Wang, Guoqiang</creator><creator>Chen, Shiqing</creator><creator>Zeng, Jian</creator><creator>Tao, Feng</creator><creator>Xu, Bichun</creator><creator>Ke, Honggang</creator><creator>Li, Mei</creator><general>Frontiers Media S.A</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20210527</creationdate><title>Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades</title><author>Wang, Xiaoyan ; Wu, Bingchen ; Yan, Zhengqing ; Wang, Guoqiang ; Chen, Shiqing ; Zeng, Jian ; Tao, Feng ; Xu, Bichun ; Ke, Honggang ; Li, Mei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-60ced903a3199573cdb4fae1d28d37d8f0f59b6efb53fc0bcf2c40c2fe9fb56a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>immune checkpoint blockades</topic><topic>JAK-STAT</topic><topic>non-small cell lung cancer</topic><topic>Oncology</topic><topic>PTPRD</topic><topic>PTPRT</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xiaoyan</creatorcontrib><creatorcontrib>Wu, Bingchen</creatorcontrib><creatorcontrib>Yan, Zhengqing</creatorcontrib><creatorcontrib>Wang, Guoqiang</creatorcontrib><creatorcontrib>Chen, Shiqing</creatorcontrib><creatorcontrib>Zeng, Jian</creatorcontrib><creatorcontrib>Tao, Feng</creatorcontrib><creatorcontrib>Xu, Bichun</creatorcontrib><creatorcontrib>Ke, Honggang</creatorcontrib><creatorcontrib>Li, Mei</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Frontiers in oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xiaoyan</au><au>Wu, Bingchen</au><au>Yan, Zhengqing</au><au>Wang, Guoqiang</au><au>Chen, Shiqing</au><au>Zeng, Jian</au><au>Tao, Feng</au><au>Xu, Bichun</au><au>Ke, Honggang</au><au>Li, Mei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades</atitle><jtitle>Frontiers in oncology</jtitle><date>2021-05-27</date><risdate>2021</risdate><volume>11</volume><spage>650122</spage><epage>650122</epage><pages>650122-650122</pages><issn>2234-943X</issn><eissn>2234-943X</eissn><abstract>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&lt;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.</abstract><pub>Frontiers Media S.A</pub><pmid>34123798</pmid><doi>10.3389/fonc.2021.650122</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2234-943X
ispartof Frontiers in oncology, 2021-05, Vol.11, p.650122-650122
issn 2234-943X
2234-943X
language eng
recordid cdi_doaj_primary_oai_doaj_org_article_01b10a7acc604c4da996add6d718bf71
source PubMed (Medline)
subjects immune checkpoint blockades
JAK-STAT
non-small cell lung cancer
Oncology
PTPRD
PTPRT
title Association of PTPRD/PTPRT Mutation With Better Clinical Outcomes in NSCLC Patients Treated With Immune Checkpoint Blockades
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T14%3A01%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Association%20of%20PTPRD/PTPRT%20Mutation%20With%20Better%20Clinical%20Outcomes%20in%20NSCLC%20Patients%20Treated%20With%20Immune%20Checkpoint%20Blockades&rft.jtitle=Frontiers%20in%20oncology&rft.au=Wang,%20Xiaoyan&rft.date=2021-05-27&rft.volume=11&rft.spage=650122&rft.epage=650122&rft.pages=650122-650122&rft.issn=2234-943X&rft.eissn=2234-943X&rft_id=info:doi/10.3389/fonc.2021.650122&rft_dat=%3Cproquest_doaj_%3E2540721436%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c439t-60ced903a3199573cdb4fae1d28d37d8f0f59b6efb53fc0bcf2c40c2fe9fb56a3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2540721436&rft_id=info:pmid/34123798&rfr_iscdi=true