title: Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing.
abstract: Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC.
authors.affiliation: Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.
authors.forename: Ke-Zhong
authors.initials: KZ
authors.lastname: Chen
authors.affiliation: Department of Bioinformatics, San Valley Biotechnology Incorporated, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lou
authors.affiliation: Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Bioinformatics, San Valley Biotechnology Incorporated, Beijing, China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Zhang
authors.affiliation: Department of Bioinformatics, San Valley Biotechnology Incorporated, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Bioinformatics, San Valley Biotechnology Incorporated, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Guan
authors.affiliation: Department of Bioinformatics, San Valley Biotechnology Incorporated, Beijing, China.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Zhao
authors.affiliation: Department of Bioinformatics, San Valley Biotechnology Incorporated, Beijing, China.
authors.forename: Xue-Xia
authors.initials: XX
authors.lastname: Su
authors.affiliation: Department of Bioinformatics, San Valley Biotechnology Incorporated, Beijing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Shi
authors.affiliation: Departments of Molecular Microbiology &Immunology and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Jones
authors.affiliation: Departments of Molecular Microbiology &Immunology and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Xue F
authors.initials: XF
authors.lastname: Huang
authors.affiliation: Departments of Molecular Microbiology &Immunology and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Si-Yi
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D018394:CA-125 Antigen / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D000074141:Circulating Tumor DNA / Q000097:blood* / Q000737:chemistry; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics; D004273:DNA, Neoplasm / Q000097:blood / Q000737:chemistry; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D000074141:Circulating Tumor DNA; D004273:DNA, Neoplasm; C117307:KRAS protein, human; C451759:MUC16 protein, human; D008565:Membrane Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C578959:carbohydrate antigen 199, human; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)