title: MACC1 mRNA levels predict cancer recurrence after resection of colorectal cancer liver metastases.
abstract: OBJECTIVE
  Upon colon cancer metastasis resection in liver, disease outcome is heterogeneous, ranging from indolent to very aggressive, with early recurrence. The aim of this study is to investigate the capability of metastasis associated in colon cancer 1 (MACC1) levels measured in liver metastasis specimens to predict further recurrence of the disease.
  
  
  METHODS
  Gene expression and gene dosage of MACC1, hepatocyte growth factor (HGF), and hepatocyte growth factor receptor (MET) were assessed using quantitative realtime polymerase chain reaction on a cohort of 64 liver metastasis samples from patients with complete follow-up of 36 months and detailed clinical annotation. The most relevant mutations associated to prognosis in colorectal cancer, KRAS, and PIK3CA were assessed on the same specimens with Sanger sequencing.
  
  
  RESULTS
  Receiver operating characteristic (ROC) analysis revealed that MACC1 mRNA abundance is a good indicator of metastatic recurrence (AUC = 0.65, P < 0.05), whereas no such results were obtained with MET and HGF, nor with gene dosage. Generation of MACC1-based risk classes was capable of successfully separating patients into poor and good prognosis subgroups [hazard ratio (HR) = 5.236, 95% confidence interval (CI) = 1.2068-22.715, P < 0.05]. Also KRAS mutation was significantly associated with higher risk of recurrence (HR = 2.07, 95% CI = 1.048-4.09, P < 0.05). Cox regression multivariate analysis supported the independence of MACC1, but not KRAS, from known prognostic clinical information (Node Size HR = 3.155, 95% CI = 1.4418-6.905, P < 0.001, Preoperative carcinoembryonic antigen HR = 2.359, 95% CI = 1.0203-5.452, P < 0.05, MACC1 HR = 7.2739, 95% CI = 1.6584-31.905, P < 0.01).
  
  
  CONCLUSIONS
  MACC1, a new easily detectable biomarker in cancer, is an independent prognostic factor of recurrence after liver resection of colorectal cancer metastasis.
authors.affiliation: Laboratory of Oncogenomics, IRC@C: Institute for Cancer Research at Candiolo, Italy. claudio.isella@ircc.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Isella
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mellano
authors.forename: Francesco
authors.initials: F
authors.lastname: Galimi
authors.forename: Consalvo
authors.initials: C
authors.lastname: Petti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Capussotti
authors.forename: Michele
authors.initials: M
authors.lastname: De Simone
authors.forename: Andrea
authors.initials: A
authors.lastname: Bertotti
authors.forename: Enzo
authors.initials: E
authors.lastname: Medico
authors.forename: Andrea
authors.initials: A
authors.lastname: Muratore
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D003952:Diagnostic Imaging; D005260:Female; D017228:Hepatocyte Growth Factor / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000556:secondary* / Q000601:surgery*; D008297:Male; D009010:Monte Carlo Method; D009154:Mutation; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger; D012372:ROC Curve; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D058534:Class I Phosphatidylinositol 3-Kinases; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D019859:Proto-Oncogene Proteins c-met; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D018631:ras Proteins; C117307:KRAS protein, human; C544162:MACC1 protein, human; C484760:PIK3CA protein, human; C491743:MET protein, human