title: S100A4 over-expression underlies lymph node metastasis and poor prognosis in colorectal cancer.
abstract: OBJECTIVE
  To develop lymph node metastasis (LNM)-associated biomarkers for colorectal cancer (CRC) using quantitative proteome analysis.
  
  
  METHODS
  Differences in protein expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed using methyl esterification stable isotope labeling coupled with 2D liquid chromatography followed by tandem mass spectrometry (2D-LC-MS/MS). The relationship to clinicopathological parameters and prognosis of candidate biomarkers was examined using an independent sample set.
  
  
  RESULTS
  Forty-three proteins were found to be differentially expressed by at least 2.5-fold in two types of CRC. S100A4 was significantly upregulated in LNM CRC compared with non-LNM CRC, which was confirmed by Western blotting, immunohistochemistry and real-time quantitative polymerase chain reaction. Further immunohistochemistry on another 112 CRC cases showed that overexpression of S100A4 frequently existed in LNM CRC compared with non-LNM CRC (P<0.001). Overexpression of S100A4 was significantly associated with LNM (P<0.001), advanced TNM stage (P<0.001), increased 5-year recurrence rate (P<0.001) and decreased 5-year overall survival rate (P<0.001). Univariate and multivariate analyses indicated that S100A4 expression was an independent prognostic factor for recurrence and survival of CRC patients (P<0.05).
  
  
  CONCLUSIONS
  S100A4 might serve as a powerful biomarker for LNM and a prognostic factor in CRC.
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
authors.forename: Li-Yong
authors.initials: LY
authors.lastname: Huang
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Guo-Xiang
authors.initials: GX
authors.lastname: Cai
authors.forename: Zu-Qing
authors.initials: ZQ
authors.lastname: Guan
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: Sheng
authors.forename: Hong-Fen
authors.initials: HF
authors.lastname: Lu
authors.forename: Li-Qi
authors.initials: LQ
authors.lastname: Xie
authors.forename: Hao-Jie
authors.initials: HJ
authors.lastname: Lu
authors.forename: San-Jun
authors.initials: SJ
authors.lastname: Cai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020543:Proteome; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human