title: Post surgery circulating free tumor DNA is a predictive biomarker for relapse of lung cancer.
abstract: Cancer cells release DNA fragments into plasma as circulating free DNA (cfDNA). However, quantitative measurement of tumor-derived DNA in cfDNA remains challenge. The purpose of this study was to quantitatively assess tumor-derived DNA in lung cancer patients. By optimizing competitive allele-specific TaqMan PCR (CAST-PCR), we assessed the copy number of mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) alleles in the pre/post surgery plasma of 168 lung cancer patients. An absolute quantitative PCR method was developed to assess the number of total cfDNA. All mutations detected in tumors were also found in the plasma after surgery. At the time of 30 days after surgery, EGFR mutation of circulating cell-free DNA was detected only in two patients who recurred in 4 months after surgery. Compared to that of normal control at 30 days after surgery, five patients who recurred in 4 months had significantly higher circulating cell-free DNA (P < 0.001), whereas six patients who recurred after 4 months (P = 0.207) and five patients without recurrence (P = 0.901) demonstrated significantly lower circulating cell-free DNA. Our findings suggest that cfDNA analysis in plasma is an alternative and supplement to tissue analysis and hold promise for clinical application. Stratification of patients according to cfDNA levels at 30 days after surgery might be helpful in selecting lung cancer patients for adjuvant therapy after surgery.
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Shanghai Pulmonary Hospital, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Longzhen
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Yin
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Huang
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Gu
authors.affiliation: Shanghai Pulmonary Hospital, Shanghai, China.
authors.forename: Gening
authors.initials: G
authors.lastname: Jiang
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.|Tongji University Suzhou Institute, Suzhou, Jiangsu, China.|Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D004273:DNA, Neoplasm / Q000097:blood*; D066246:ErbB Receptors / Q000097:blood / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000097:blood / Q000235:genetics*; D012008:Recurrence
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C117307:KRAS protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Circulating cell-free DNA; lung cancer; relapse; surgery