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Titin mutation in circulatory tumor DNA is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer

BACKGROUND: Only a fraction of patients with advanced non-small cell lung cancer (NSCLC) respond well to immune checkpoint blockade (ICB) therapy. Here, we investigated whether Titin (TTN) mutation, which has been demonstrated to be a predictive biomarker in tissue-based analysis, can identify patie...

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Autores principales: Su, Chunxia, Wang, Xinxin, Zhou, Juan, Zhao, Jing, Zhou, Fei, Zhao, Guodong, Xu, Xiaohong, Zou, Xuan, Zhu, Bo, Jia, Qingzhu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044474/
https://www.ncbi.nlm.nih.gov/pubmed/33889507
http://dx.doi.org/10.21037/tlcr-20-1118
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author Su, Chunxia
Wang, Xinxin
Zhou, Juan
Zhao, Jing
Zhou, Fei
Zhao, Guodong
Xu, Xiaohong
Zou, Xuan
Zhu, Bo
Jia, Qingzhu
author_facet Su, Chunxia
Wang, Xinxin
Zhou, Juan
Zhao, Jing
Zhou, Fei
Zhao, Guodong
Xu, Xiaohong
Zou, Xuan
Zhu, Bo
Jia, Qingzhu
author_sort Su, Chunxia
collection PubMed
description BACKGROUND: Only a fraction of patients with advanced non-small cell lung cancer (NSCLC) respond well to immune checkpoint blockade (ICB) therapy. Here, we investigated whether Titin (TTN) mutation, which has been demonstrated to be a predictive biomarker in tissue-based analysis, can identify patients with a greater likelihood in response to ICB based on circulatory tumor DNA (ctDNA) sequencing. METHODS: In this retrospective analysis, 92 patients with advanced NSCLC from two independent cohorts who received ICB treatment were included. A probe panel covering all exons of TTN was developed and validated to detect TTN mutation in ctDNA. Baseline plasma samples were collected and subjected to ctDNA sequencing with the TTN probe panel. RESULTS: Of the 92 patients, 28.3% harbored TTN mutation in their baseline ctDNA. Progression-free survival was significantly improved in patients with the mutated TTN (212 days and 334.5 days for cohort 1 and 2) compared to those without the mutation (113 days and 147 days for cohort 1 and 2). Objective response to ICB treatment (40% for TTN(mut) and 15.8% for TTN(wt) in cohort 1; 50% for TTN(mut) and 23.4% for TTN(wt) in cohort 2) was common in patients with mutated TTN. Stratified analysis showed a generally predictive potential of TTN mutation in patients with advanced NSCLC. CONCLUSIONS: The presence of mutated TTN in pre-treatment peripheral blood was associated with favorable objective response and survival with ICB administration. Therefore, circulatory TTN mutation may be applicable for guiding ICB immunotherapy in patients with NSCLC.
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spelling pubmed-80444742021-04-21 Titin mutation in circulatory tumor DNA is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer Su, Chunxia Wang, Xinxin Zhou, Juan Zhao, Jing Zhou, Fei Zhao, Guodong Xu, Xiaohong Zou, Xuan Zhu, Bo Jia, Qingzhu Transl Lung Cancer Res Original Article BACKGROUND: Only a fraction of patients with advanced non-small cell lung cancer (NSCLC) respond well to immune checkpoint blockade (ICB) therapy. Here, we investigated whether Titin (TTN) mutation, which has been demonstrated to be a predictive biomarker in tissue-based analysis, can identify patients with a greater likelihood in response to ICB based on circulatory tumor DNA (ctDNA) sequencing. METHODS: In this retrospective analysis, 92 patients with advanced NSCLC from two independent cohorts who received ICB treatment were included. A probe panel covering all exons of TTN was developed and validated to detect TTN mutation in ctDNA. Baseline plasma samples were collected and subjected to ctDNA sequencing with the TTN probe panel. RESULTS: Of the 92 patients, 28.3% harbored TTN mutation in their baseline ctDNA. Progression-free survival was significantly improved in patients with the mutated TTN (212 days and 334.5 days for cohort 1 and 2) compared to those without the mutation (113 days and 147 days for cohort 1 and 2). Objective response to ICB treatment (40% for TTN(mut) and 15.8% for TTN(wt) in cohort 1; 50% for TTN(mut) and 23.4% for TTN(wt) in cohort 2) was common in patients with mutated TTN. Stratified analysis showed a generally predictive potential of TTN mutation in patients with advanced NSCLC. CONCLUSIONS: The presence of mutated TTN in pre-treatment peripheral blood was associated with favorable objective response and survival with ICB administration. Therefore, circulatory TTN mutation may be applicable for guiding ICB immunotherapy in patients with NSCLC. AME Publishing Company 2021-03 /pmc/articles/PMC8044474/ /pubmed/33889507 http://dx.doi.org/10.21037/tlcr-20-1118 Text en 2021 Translational Lung Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Su, Chunxia
Wang, Xinxin
Zhou, Juan
Zhao, Jing
Zhou, Fei
Zhao, Guodong
Xu, Xiaohong
Zou, Xuan
Zhu, Bo
Jia, Qingzhu
Titin mutation in circulatory tumor DNA is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer
title Titin mutation in circulatory tumor DNA is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer
title_full Titin mutation in circulatory tumor DNA is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer
title_fullStr Titin mutation in circulatory tumor DNA is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer
title_full_unstemmed Titin mutation in circulatory tumor DNA is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer
title_short Titin mutation in circulatory tumor DNA is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer
title_sort titin mutation in circulatory tumor dna is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044474/
https://www.ncbi.nlm.nih.gov/pubmed/33889507
http://dx.doi.org/10.21037/tlcr-20-1118
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