title: Combined phenotype of 4 markers improves prognostic value of patients with colon cancer.
abstract: BACKGROUND
  Combination of multiple biomarkers representing distinct aspects of tumor biology will have a better prognostic value. This study was to identify prognostic subgroups of colon adenocarcinoma by combined analysis of synuclein-gamma (SNCG), a human homologue of piwi (Hiwi), phosphatase of regenerating liver-3 (PRL-3), arrest-defective protein 1, homolog A (ARD1) and clinicopathologic features in 225 colon adenocarcinoma specimens.
  
  
  METHODS
  Immunohistochemistry for 4 tumor markers was performed in whole tissue sections from 225 colon adenocarcinoma patients with complete clinicopathologic data and up to 10-year follow-up. The immunohistochemical expression patterns were examined individually and in multimarker combinations. Univariate and multivariate analyses were performed to identify independent predictive markers of poor outcome.
  
  
  RESULTS
  With the tumor marker positive rate [32.0% (62/225) for SNCG; 76.9% (173/225) for combined SNCG/Hiwi/PRL-3/ARD1] and the detecting accuracy [61.9% (252/407) for SNCG; 82.6% (336/407) for combined SNCG/Hiwi/PRL-3/ARD1] increasing, incremental value of combined SNCG/Hiwi/PRL-3/ARD1 (P < 0.001; hazard ratios (HR), 3.2) to poor outcome was found. Stratified by lymph node, Hiwi alone (P = 0.004; HR, 3.2) led to poor outcome in patients without lymph node metastasis (LN-), and SNCG (P < 0.001; HR, 2.5) had independently poor prognostic value for patients with lymph node metastasis (LN+).
  
  
  CONCLUSIONS
  Multimarker phenotypes improved tumor positive rate, detecting accuracy and prognostic value. In addition, a subgroup of more aggressive tumors can be identified by evaluating Hiwi level in LN- cancer, and SNCG level in LN+ cancer.
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, Haidian District, Beijing, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Liu
authors.forename: Like
authors.initials: L
authors.lastname: Qu
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Xing
authors.forename: Tingting
authors.initials: T
authors.lastname: Ren
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.forename: Beihai
authors.initials: B
authors.lastname: Jiang
authors.forename: Lin
authors.initials: L
authors.lastname: Meng
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Chengchao
authors.initials: C
authors.lastname: Shou
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060565:Argonaute Proteins / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D004722:Endoribonucleases / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D051845:gamma-Synuclein / Q000235:genetics*
chemical_list: D060565:Argonaute Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C421088:PIWIL1 protein, human; D016601:RNA-Binding Proteins; C104249:SNCG protein, human; D051845:gamma-Synuclein; D004722:Endoribonucleases; D010749:Phosphoprotein Phosphatases; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases; C097081:PPP1R8 protein, human