Association between plasma somatic copy number variations and response to immunotherapy in patients with programmed death-ligand 1-negative non-small cell lung cancer

Objective To determine how patients with non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1)-negative and/or a low tumor mutation burden status benefit from immune checkpoint inhibitors (ICI). Methods We determined the plasma cell-free DNA profiles of 25 patients with PD-L1-neg...

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Published in:Journal of international medical research 2022-04, Vol.50 (4), p.3000605221093222-3000605221093222
Main Authors: Zhang, Xiaochen, Wang, Yina, Xiang, Jingjing, Zhao, Pan, Xun, Yanping, Zhang, Shirong, Xu, Nong
Format: Article
Language:English
Subjects:
B7-H1 Antigen - genetics
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
DNA Copy Number Variations - genetics
Humans
Immunotherapy
Ligands
Lung cancer
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Pre-Clinical Research Report
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container_title Journal of international medical research
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creator Zhang, Xiaochen
Wang, Yina
Xiang, Jingjing
Zhao, Pan
Xun, Yanping
Zhang, Shirong
Xu, Nong
description Objective To determine how patients with non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1)-negative and/or a low tumor mutation burden status benefit from immune checkpoint inhibitors (ICI). Methods We determined the plasma cell-free DNA profiles of 25 patients with PD-L1-negative advanced NSCLC before ICI therapy using low-coverage whole-genome sequencing. Results Elevated cell-free copy number variations (CNVs) were associated with progressive disease, with a cutoff CNV score of 0.10 evaluated with an area under the curve of 0.790 in PD-L1-negative NSCLC. CNV changes were also correlated with poor survival. Progression-free survival and overall survival were both significantly shorter in CNVhigh compared with CNVlow patients. Conclusions Cell-free CNV may be a useful peripheral blood biomarker for predicting the response to ICIs in patients with NSCLC.
doi_str_mv 10.1177/03000605221093222
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Methods We determined the plasma cell-free DNA profiles of 25 patients with PD-L1-negative advanced NSCLC before ICI therapy using low-coverage whole-genome sequencing. Results Elevated cell-free copy number variations (CNVs) were associated with progressive disease, with a cutoff CNV score of 0.10 evaluated with an area under the curve of 0.790 in PD-L1-negative NSCLC. CNV changes were also correlated with poor survival. Progression-free survival and overall survival were both significantly shorter in CNVhigh compared with CNVlow patients. Conclusions Cell-free CNV may be a useful peripheral blood biomarker for predicting the response to ICIs in patients with NSCLC.</description><identifier>ISSN: 0300-0605</identifier><identifier>EISSN: 1473-2300</identifier><identifier>DOI: 10.1177/03000605221093222</identifier><identifier>PMID: 35466753</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>B7-H1 Antigen - genetics ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; DNA Copy Number Variations - genetics ; Humans ; Immunotherapy ; Ligands ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Pre-Clinical Research Report</subject><ispartof>Journal of international medical research, 2022-04, Vol.50 (4), p.3000605221093222-3000605221093222</ispartof><rights>The Author(s) 2022</rights><rights>The Author(s) 2022. This work is licensed under the Creative Commons Attribution – Non-Commercial License https://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2022 2022 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4472-4fb66d05557bab0729c8458f43776d5d2c5d4b78939e8473056735f2c94c9cbb3</citedby><cites>FETCH-LOGICAL-c4472-4fb66d05557bab0729c8458f43776d5d2c5d4b78939e8473056735f2c94c9cbb3</cites><orcidid>0000-0001-9334-1637</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047987/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2661415826?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,21944,25730,27829,27900,27901,36988,36989,44565,44920,45308,53765,53767</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35466753$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Xiaochen</creatorcontrib><creatorcontrib>Wang, Yina</creatorcontrib><creatorcontrib>Xiang, Jingjing</creatorcontrib><creatorcontrib>Zhao, Pan</creatorcontrib><creatorcontrib>Xun, Yanping</creatorcontrib><creatorcontrib>Zhang, Shirong</creatorcontrib><creatorcontrib>Xu, Nong</creatorcontrib><title>Association between plasma somatic copy number variations and response to immunotherapy in patients with programmed death-ligand 1-negative non-small cell lung cancer</title><title>Journal of international medical research</title><addtitle>J Int Med Res</addtitle><description>Objective To determine how patients with non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1)-negative and/or a low tumor mutation burden status benefit from immune checkpoint inhibitors (ICI). Methods We determined the plasma cell-free DNA profiles of 25 patients with PD-L1-negative advanced NSCLC before ICI therapy using low-coverage whole-genome sequencing. Results Elevated cell-free copy number variations (CNVs) were associated with progressive disease, with a cutoff CNV score of 0.10 evaluated with an area under the curve of 0.790 in PD-L1-negative NSCLC. CNV changes were also correlated with poor survival. Progression-free survival and overall survival were both significantly shorter in CNVhigh compared with CNVlow patients. 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subjects B7-H1 Antigen - genetics
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - genetics
DNA Copy Number Variations - genetics
Humans
Immunotherapy
Ligands
Lung cancer
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Pre-Clinical Research Report
title Association between plasma somatic copy number variations and response to immunotherapy in patients with programmed death-ligand 1-negative non-small cell lung cancer
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