title: An integrated proteomics and metabolomics approach for defining oncofetal biomarkers in the colorectal cancer.
abstract: OBJECTIVE
  The present study was designed to search for potential diagnostic biomarkers in the serum of colorectal cancer (CRC).
  
  
  BACKGROUND
  CRC is the third most common cancer worldwide, and its prognosis is poor at early stages. A panel of novel biomarkers is urgently needed for early diagnosis of CRC.
  
  
  METHODS
  An integrated proteomics and metabolomics approach was performed to define oncofetal biomarkers in CRC by protein and metabolite profiling of serum samples from CRC patients, healthy control adults, and fetus. The differentially expressed proteins were identified by a 2-D DIGE (2-Dimensional Difference Gel Electrophoresis) coupled with a Finnigan LTQ-based proteomics approach. Meanwhile, the serum metabolome was analyzed using gas chromatography-mass spectrometry integrated with a commercial mass spectral library for peak identification.
  
  
  RESULTS
  Of the 28 identified proteins and the 34 analyzed metabolites, only 5 protein spots and 6 metabolites were significantly increased or decreased in both CRC and fetal serum groups compared with the healthy adult group. Data from supervised predictive models allowed a separation of 93.5% of CRC patients from the healthy controls using the 6 metabolites. Finally, correlation analysis was applied to establish quantitative linkages between the 5 individual metabolite 3-hydroxybutyric acid, L-valine, L-threonine, 1-deoxyglucose, and glycine and the 5 individual proteins MACF1, APOH, A2M, IGL@, and VDB. Furthermore, 10 potential oncofetal biomarkers were characterized and their potential for CRC diagnosis was validated.
  
  
  CONCLUSIONS
  The integrated approach we developed will promote the translation of biomarkers with clinical value into routine clinical practice.
authors.affiliation: Department of Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, People's Republic of China. yanleima@live.cn
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Ma
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Weijie
authors.initials: W
authors.lastname: Liu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yang
authors.forename: Huanlong
authors.initials: H
authors.lastname: Qin
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D055432:Metabolomics; D016571:Neural Networks, Computer; D040901:Proteomics; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D014408:Biomarkers, Tumor