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The diagnostic value of circulating tumor cells and ctDNA for gene mutations in lung cancer

Authors Lyu M, Zhou J, Ning K, Ying B

Received 20 November 2018

Accepted for publication 14 February 2019

Published 5 April 2019 Volume 2019:12 Pages 2539—2552


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Leo Jen-Liang Su

Mengyuan Lyu,1,2,* Jian Zhou,1,3,* Kang Ning,1 Binwu Ying2

1West China School of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China

*These authors contributed equally to this work

Purpose: Detecting gene mutations by two competing biomarkers, circulating tumor cells (CTCs) and ctDNA has gradually paved a new diagnostic avenue for personalized medicine. We performed a comprehensive analysis to compare the diagnostic value of CTCs and ctDNA for gene mutations in lung cancer.
Methods: Publications were electronically searched in PubMed, Embase, and Web of Science as of July 2018. Pooled sensitivity, specificity, and AUC, each with a 95% CI, were yielded. Subgroup analyses and sensitivity analyses were conducted. Quality assessment of included studies was also performed.
Results: From 4,283 candidate articles, we identified 47 articles with a total of 7,244 patients for qualitative review and meta-analysis. When detecting EGFR, the CTC and ctDNA groups had pooled sensitivity of 75.4% (95% CI 0.683–0.817) and 67.1% (95% CI 0.647–0.695), respectively. When testing KRAS, pooled sensitivity was 38.7% (95% CI 0.266–0.519) in the CTC group and 65.1% (95% CI 0.558–0.736) in the ctDNA group. The diagnostic performance of ctDNA in testing ALK and BRAF was also evaluated. Heterogeneity among the 47 articles was acceptable.
Conclusion: ctDNA might be a more promising biomarker with equivalent performance to CTCs when detecting EGFR and its detailed subtypes, and superior diagnostic capacity when testing KRAS and ALK. In addition, the diagnostic performance of ctDNA and CTCs depends on the detection methods greatly, and this warrants further studies to explore more sensitive methods.

Keywords: lung cancer, circulating tumor cell, circulating tumor DNA, gene mutations

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