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Article type: Research Article
Authors: Zhang, Haoa; 1 | He, Bina; 1 | Cui, Juna | Zhao, Mingzhangb; * | Zhang, Zengwanga; *
Affiliations: [a] Centre for Cardiothoracic Surgery, Xiangyang Central Hospital, Hospital Affiliated to Hubei University of Arts and Science, Xiangyang 441021, Hubei, China | [b] General Thoracic Surgery, Yicheng People’s Hospital, Xiangyang 441400, Hubei, China
Correspondence: [*] Corresponding authors: Mingzhang Zhao, General Thoracic Surgery, Yicheng People’s Hospital, Yicheng People’s Road 10, Xiangyang 441400, Hubei, China. E-mail: [email protected],CentreforCardiothoracicSurgery,XiangyangCentralHospital,HospitalAffiliatedtoHubeiUniversityofArtsandScience,Xiangyang441021,Hubei,China.E-mail:[email protected].
Note: [1] Both authors contributed equally.
Abstract: PURPOSE: The need for less invasive procedures for lung cancer probing is critically needed to better understand the disease. The purpose of the current study aims to explore the use of circulating tumor DNA (ctDNA) derived from plasma and urine specimens. METHODS: Matched peripheral blood and morning urine specimens were obtained from 160 late stage NSCLC patients. The amount of ctDNA was quantified for each of the patients. Activating and sensitizing EGFR mutations commonly found in NSCLC patients were profiled. Longitudinal analysis was performed to compared DNA variations during disease progression. RESULTS: Measurement of EGFR mutations in NSCLC patients using plasma and urinal DNA demonstrated strong concordance to conventional tissue biopsy profiling. Baseline matched tumor samples yielded 82.8% and 84.0% for plasma and urinal DNA respectively. For these measurements, the positive predictive value was 100% for plasma and urinal DNA. In the longitudinal study, we observed strong links to disease severity and survival analysis showed a clear trend with patients having higher DNA concentrations to have worse outcome especially for urinal DNA. HR for patients stratified using plasma and urinal DNA were 1.23 and 2.55 respectively. CONCLUSION: Measurements of circulating DNA within body fluids presented potentially new tools for the disease management of NSCLC patients with EGFR mutations. We demonstrated both plasma and urinal DNA correlated well to tissue biopsies and were potentially prognostic to address patients’ survival outcome.
Keywords: NSCLC, ctDNA, EGFR, T790M, plasma DNA, urinal DNA
DOI: 10.3233/CBM-181511
Journal: Cancer Biomarkers, vol. 23, no. 3, pp. 427-436, 2018
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