Malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profiling

Background The clinical utility of malignant pleural effusion (MPE) to detect mutation has been well documented; however, routine practice of the use of MPE involves collection of the cell pellet to detect mutation, and limited studies have interrogated the MPE supernatant as an alternative source o...

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Main Authors: Zhihua Guo, Zhanhong Xie, Huifang Shi, Wei Du, Lijun Peng, Wei Han, Feidie Duan, Xin Zhang, Mingyan Chen, Junli Duan, Jing Lin, Xuewei Chen, Analyn Ang Lizaso, Han Han‐Zhang, Jianxing He, Weiqiang Yin
Format: Article
Language:English
Published: Wiley 2019-04-01
Series:Thoracic Cancer
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Online Access:https://doi.org/10.1111/1759-7714.13006
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author Zhihua Guo
Zhanhong Xie
Huifang Shi
Wei Du
Lijun Peng
Wei Han
Feidie Duan
Xin Zhang
Mingyan Chen
Junli Duan
Jing Lin
Xuewei Chen
Analyn Ang Lizaso
Han Han‐Zhang
Jianxing He
Weiqiang Yin
author_facet Zhihua Guo
Zhanhong Xie
Huifang Shi
Wei Du
Lijun Peng
Wei Han
Feidie Duan
Xin Zhang
Mingyan Chen
Junli Duan
Jing Lin
Xuewei Chen
Analyn Ang Lizaso
Han Han‐Zhang
Jianxing He
Weiqiang Yin
author_sort Zhihua Guo
collection DOAJ
description Background The clinical utility of malignant pleural effusion (MPE) to detect mutation has been well documented; however, routine practice of the use of MPE involves collection of the cell pellet to detect mutation, and limited studies have interrogated the MPE supernatant as an alternative source of tumor‐derived DNA for mutation profiling. In this study, we investigated the potential of MPE supernatant as a liquid biopsy specimen by comparing its mutation profile with that of matched MPE cell pellets, tissue, and plasma samples. Methods Sequencing data from 17 patients with matched lung tissue, plasma, and MPE samples were retrospectively analyzed. Capture‐based targeted sequencing was performed on matched plasma and MPE supernatant samples obtained from 154 patients with advanced lung adenocarcinoma. Results MPE supernatants had significantly higher median maximum allelic fractions (maxAFs) than their corresponding cell pellets (P = 0.008) and plasma samples (P = 0.036), and a comparable maxAF value to that of tissue samples (P = 0.675). Comparison of MPE supernatant and matched plasma samples from the larger cohort (n = 154) revealed a comparable mutation detection rate; however, MPE supernatant had a significantly higher median maxAF than plasma (20.3% vs. 1.13%; P < 0.001). Furthermore, the concordance rates between MPE supernatant and plasma for single‐nucleotide and copy number variations were 56% and 18%, respectively, suggesting that MPE supernatant reveals a more comprehensive mutation spectrum, particularly for copy number variations. Conclusion Overall, our study shows that MPE supernatant is an optimal alternative source of tumor‐derived DNA for comprehensive mutation profiling.
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spelling doaj.art-d6fbe50dea2341919c0a492ab21923232023-04-17T06:34:28ZengWileyThoracic Cancer1759-77061759-77142019-04-0110482383110.1111/1759-7714.13006Malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profilingZhihua Guo0Zhanhong Xie1Huifang Shi2Wei Du3Lijun Peng4Wei Han5Feidie Duan6Xin Zhang7Mingyan Chen8Junli Duan9Jing Lin10Xuewei Chen11Analyn Ang Lizaso12Han Han‐Zhang13Jianxing He14Weiqiang Yin15Department of Cardiothoracic Surgery The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaDepartment of Cardiothoracic Surgery The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaDepartment of Respiratory Medicine, The Second Affiliated Hospital of Hainan Medical University Haikou ChinaGeneral Hospital of Southern Theater Command, PLA Guangzhou ChinaGeneral Hospital of Southern Theater Command, PLA Guangzhou ChinaBurning Rock Biotech Guangzhou ChinaDepartment of Respiratory Medicine, The Second Affiliated Hospital of Hainan Medical University Haikou ChinaDepartment of Cardiothoracic Surgery The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaBurning Rock Biotech Guangzhou ChinaBurning Rock Biotech Guangzhou ChinaBurning Rock Biotech Guangzhou ChinaDepartment of Cardiothoracic Surgery The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaBurning Rock Biotech Guangzhou ChinaBurning Rock Biotech Guangzhou ChinaDepartment of Cardiothoracic Surgery The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaDepartment of Cardiothoracic Surgery The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaBackground The clinical utility of malignant pleural effusion (MPE) to detect mutation has been well documented; however, routine practice of the use of MPE involves collection of the cell pellet to detect mutation, and limited studies have interrogated the MPE supernatant as an alternative source of tumor‐derived DNA for mutation profiling. In this study, we investigated the potential of MPE supernatant as a liquid biopsy specimen by comparing its mutation profile with that of matched MPE cell pellets, tissue, and plasma samples. Methods Sequencing data from 17 patients with matched lung tissue, plasma, and MPE samples were retrospectively analyzed. Capture‐based targeted sequencing was performed on matched plasma and MPE supernatant samples obtained from 154 patients with advanced lung adenocarcinoma. Results MPE supernatants had significantly higher median maximum allelic fractions (maxAFs) than their corresponding cell pellets (P = 0.008) and plasma samples (P = 0.036), and a comparable maxAF value to that of tissue samples (P = 0.675). Comparison of MPE supernatant and matched plasma samples from the larger cohort (n = 154) revealed a comparable mutation detection rate; however, MPE supernatant had a significantly higher median maxAF than plasma (20.3% vs. 1.13%; P < 0.001). Furthermore, the concordance rates between MPE supernatant and plasma for single‐nucleotide and copy number variations were 56% and 18%, respectively, suggesting that MPE supernatant reveals a more comprehensive mutation spectrum, particularly for copy number variations. Conclusion Overall, our study shows that MPE supernatant is an optimal alternative source of tumor‐derived DNA for comprehensive mutation profiling.https://doi.org/10.1111/1759-7714.13006Cell‐free DNAliquid biopsylung cancermalignant pleural effusionMPE supernatant
spellingShingle Zhihua Guo
Zhanhong Xie
Huifang Shi
Wei Du
Lijun Peng
Wei Han
Feidie Duan
Xin Zhang
Mingyan Chen
Junli Duan
Jing Lin
Xuewei Chen
Analyn Ang Lizaso
Han Han‐Zhang
Jianxing He
Weiqiang Yin
Malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profiling
Thoracic Cancer
Cell‐free DNA
liquid biopsy
lung cancer
malignant pleural effusion
MPE supernatant
title Malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profiling
title_full Malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profiling
title_fullStr Malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profiling
title_full_unstemmed Malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profiling
title_short Malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profiling
title_sort malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profiling
topic Cell‐free DNA
liquid biopsy
lung cancer
malignant pleural effusion
MPE supernatant
url https://doi.org/10.1111/1759-7714.13006
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