title: Detection of cancer specific mutations in early-stage non-small cell lung cancer using cell-free DNA by targeted sequencing.
abstract: Non-small cell lung cancer (NSCLC) is a major public health problem worldwide and leads to a high mortality. NSCLC is always diagnosed in late stages because of its unapparent symptoms. However, cell-free DNA (cfDNA) may serve as a new potential biomarker to detect early stage of non‑small cell lung cancer. Here we recruited 10 non-small cell lung cancer patients to obtain fresh tumor tissue, peripheral blood lymphocytes (PBLs), and plasma. CfDNAs from 13 elderly people and 7 middle-age smokers were also extracted as controls. Illumina HiSeq X10 was used to perform next-generation sequencing to evaluate differences in mutations among different samples. The result indicated that tumor DNA and its matched plasma cfDNA samples showed high concordance in their mutation patterns. Mutation rate of cfDNA was generally lower than that of tumor tissue and higher than that of PBLs. The plasma cfDNA concentration of NSCLC patients (69.2±46.9 ng/ml) is significantly higher than that of elderly people (32.5±5.2 ng/ml, t=2.96, p=0.007) and middle-aged smokers (17.9±9.1 ng/ml, t=2.83, p=0.013). Five mutations (PTEN_c.1375A>G, TP53_c.94G>A, STK11_c.816C>T, PIK3CA_c.1633 G>A, PIK3CA_c.2038G>C) were only identified in NSCLC patients but not in healthy people. Our conclusion was that cfDNA has a similar mutation pattern with its matched tumor tissue DNA. A high concentration of cfDNA and tumor specific mutations in cfDNA may serve as potential non-invasive biomarkers to detect early-stage non‑small cell lung cancer.
authors.affiliation: The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Yutong
authors.initials: Y
authors.lastname: He
authors.affiliation: Institute of Genecrab Precision Medicine, Beijing 100078, P.R. China.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Jifang
authors.initials: J
authors.lastname: Yao
authors.affiliation: The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Yueping
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, Beijing Hospital, Beijing 100730, P.R. China.
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Min
authors.affiliation: The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, Hebei 050011, P.R. China.
authors.forename: Baoen
authors.initials: B
authors.lastname: Shan
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000230:Adenocarcinoma / Q000235:genetics*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000091162:AMP-Activated Protein Kinase Kinases; D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D004273:DNA, Neoplasm; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C484760:PIK3CA protein, human; C109790:STK11 protein, human; C494929:PTEN protein, human