Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non-small cell lung cancer

Abstract. Background:. Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lun...

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Main Authors: Weijia Huang, Kai Xu, Zhenkun Liu, Yifeng Wang, Zijia Chen, Yanyun Gao, Renwang Peng, Qinghua Zhou, Xiangxiang Pan
Format: Article
Language:English
Published: Wolters Kluwer 2025-04-01
Series:Chinese Medical Journal
Online Access:http://journals.lww.com/10.1097/CM9.0000000000003117
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author Weijia Huang
Kai Xu
Zhenkun Liu
Yifeng Wang
Zijia Chen
Yanyun Gao
Renwang Peng
Qinghua Zhou
Xiangxiang Pan
author_facet Weijia Huang
Kai Xu
Zhenkun Liu
Yifeng Wang
Zijia Chen
Yanyun Gao
Renwang Peng
Qinghua Zhou
Xiangxiang Pan
author_sort Weijia Huang
collection DOAJ
description Abstract. Background:. Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. Methods:. Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen’s kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. Results:. A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. Conclusion:. ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.
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spelling doaj-art-e867a0e5fdae45f1a08956d6dd6f54d72025-08-20T02:25:43ZengWolters KluwerChinese Medical Journal0366-69992542-56412025-04-01138785185810.1097/CM9.0000000000003117202504050-00009Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non-small cell lung cancerWeijia Huang0Kai Xu1Zhenkun Liu2Yifeng Wang3Zijia Chen4Yanyun Gao5Renwang Peng6Qinghua Zhou7Xiangxiang Pan1 Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China1 Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China1 Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China1 Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China1 Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China3 Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland3 Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Bern 3010, Switzerland1 Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, ChinaAbstract. Background:. Molecular subtyping is an essential complementarity after pathological analyses for targeted therapy. This study aimed to investigate the consistency of next-generation sequencing (NGS) results between circulating tumor DNA (ctDNA)-based and tissue-based in non-small cell lung cancer (NSCLC) and identify the patient characteristics that favor ctDNA testing. Methods:. Patients who diagnosed with NSCLC and received both ctDNA- and cancer tissue-based NGS before surgery or systemic treatment in Lung Cancer Center, Sichuan University West China Hospital between December 2017 and August 2022 were enrolled. A 425-cancer panel with a HiSeq 4000 NGS platform was used for NGS. The unweighted Cohen’s kappa coefficient was employed to discriminate the high-concordance group from the low-concordance group with a cutoff value of 0.6. Six machine learning models were used to identify patient characteristics that relate to high concordance between ctDNA-based and tissue-based NGS. Results:. A total of 85 patients were enrolled, of which 22.4% (19/85) had stage III disease and 56.5% (48/85) had stage IV disease. Forty-four patients (51.8%) showed consistent gene mutation types between ctDNA-based and tissue-based NGS, while one patient (1.2%) tested negative in both approaches. Patients with advanced diseases and metastases to other organs would be suitable for the ctDNA-based NGS, and the generalized linear model showed that T stage, M stage, and tumor mutation burden were the critical discriminators to predict the consistency of results between ctDNA-based and tissue-based NGS. Conclusion:. ctDNA-based NGS showed comparable detection performance in the targeted gene mutations compared with tissue-based NGS, and it could be considered in advanced or metastatic NSCLC.http://journals.lww.com/10.1097/CM9.0000000000003117
spellingShingle Weijia Huang
Kai Xu
Zhenkun Liu
Yifeng Wang
Zijia Chen
Yanyun Gao
Renwang Peng
Qinghua Zhou
Xiangxiang Pan
Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non-small cell lung cancer
Chinese Medical Journal
title Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non-small cell lung cancer
title_full Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non-small cell lung cancer
title_fullStr Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non-small cell lung cancer
title_full_unstemmed Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non-small cell lung cancer
title_short Circulating tumor DNA- and cancer tissue-based next-generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non-small cell lung cancer
title_sort circulating tumor dna and cancer tissue based next generation sequencing reveals comparable consistency in targeted gene mutations for advanced or metastatic non small cell lung cancer
url http://journals.lww.com/10.1097/CM9.0000000000003117
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