title: Identification of urine protein biomarkers with the potential for early detection of lung cancer.
abstract: Lung cancer is the leading cause of cancer-related deaths and has an overall 5-year survival rate lower than 15%. Large-scale clinical trials have demonstrated a significant relative reduction in mortality in high-risk individuals with low-dose computed tomography screening. However, biomarkers capable of identifying the most at-risk population and detecting lung cancer before it becomes clinically apparent are urgently needed in the clinic. Here, we report the identification of urine biomarkers capable of detecting lung cancer. Using the well-characterized inducible Kras (G12D) mouse model of lung cancer, we identified alterations in the urine proteome in tumor-bearing mice compared with sibling controls. Marked differences at the proteomic level were also detected between the urine of patients and that of healthy population controls. Importantly, we identified 7 proteins commonly found to be significantly up-regulated in both tumor-bearing mice and patients. In an independent cohort, we showed that 2 of the 7 proteins were up-regulated in urine samples from lung cancer patients but not in those from controls. The kinetics of these proteins correlated with the disease state in the mouse model. These tumor biomarkers could potentially aid in the early detection of lung cancer.
authors.affiliation: School of Life Science, Tsinghua University, Beijing 100084, China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Xijing Hospital, Xi'an 510060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cao
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Xijing Hospital, Xi'an 510060, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Xijing Hospital, Xi'an 510060, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: General Hospital of the People's Liberation Army, Beijing 100853, China.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Huanwei
authors.initials: H
authors.lastname: Huang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Mengqiu
authors.initials: M
authors.lastname: Dong
authors.affiliation: Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Xijing Hospital, Xi'an 510060, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.|National Institute of Biological Sciences, Beijing, Collaborative Innovation Center for Cancer Medicine, Beijing 102206, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000302:isolation & purification / Q000652:urine*; D045744:Cell Line, Tumor; D055088:Early Detection of Cancer; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000652:urine*; D006801:Humans; D007136:Immunoglobulins / Q000652:urine*; D008175:Lung Neoplasms / Q000235:genetics / Q000652:urine*; D051379:Mice; D040901:Proteomics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C048566:A1BG protein, human; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D007136:Immunoglobulins; C015246:LRG1 protein, human; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)