Ultra-Short Circulating Tumor DNA (usctDNA) in Plasma and Saliva of Non-Small Cell Lung Cancer (NSCLC) Patients

Cancers

Qingxiang Yan¹  Ziding Feng¹  Chien-Chung Lin²  Wu-Chou Su²  Wei-Lun Huang²  Wei Liao³  Jason H. Tang³  Macy M. Shen³  Feng Li³  Fang Wei³  Yong Kim³  Michael Tu³  Liang Li³  David Chia³  David T.W. Wong³ 

[1] Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan;School of Dentistry, University of California Los Angeles, Los Angeles, CA 90095, USA;

关键词: EFIRM;    liquid biopsy;    non-small cell lung carcinoma;    usctDNA;    EGFR mutation;   

DOI  :  10.3390/cancers12082041

来源: DOAJ

【 摘 要 】

Mutations identified in the epidermal growth factor receptor (EGFR) predict sensitivity to EGFR-targeted therapy for non-small cell lung carcinoma (NSCLC). We previously reported that Electric Field-Induced Release and Measurement (EFIRM)-based liquid biopsy could detect EGFR ctDNA with >94% concordance with tissue-based genotyping. A side-by-side comparison of concordance of EFIRM and droplet digital PCR (ddPCR) for the detection of the two front-line actionable EFGR mutations was performed with paired plasma and saliva samples from 13 NSCLC patients. Deep sequencing analysis based on single-strand DNA library preparation was employed to determine the size distributions of EGFR L858R ctDNA in plasma and saliva samples. EFIRM detected both EGFR mutations with 100% sensitivity in both plasma and saliva samples, whereas ddPCR detected EGFR mutations with sensitivities of 84.6% and 15.4%, respectively. In saliva samples, the majority of EGFR L858R ctDNA fragments detected were <80 bp. Deep sequencing analysis of ctDNA enriched for the EGFR L858R mutation revealed the significant presence of EGFR L858R ctDNA as ultra-short circulating tumor DNA (usctDNA) with the size of 40–60 bp in patient plasma and saliva. Most of usctDNAs are not amplifiable with the current ddPCR assay. Further examination using cell lines and patient biofluids revealed that the majority of usctDNAs were predominately localized in the exosomal fraction. Our study revealed the abundant existence of EGFR ctDNA in the plasma and saliva of NSCLC patients is usctDNA. usctDNA is a novel type of targets for liquid biopsy that can be efficiently detected by EFIRM technology.

【 授权许可】

Unknown