期刊
ANNALS OF SURGERY
卷 257, 期 6, 页码 1089-1095出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SLA.0b013e31828f96bc
关键词
biomarker; cancer recurrence; colorectal cancer; liver metastasis; MACC1; prognosis
类别
资金
- AIRC (Associazione Italiana per la Ricerca sul Cancro-2010 Special Program Molecular Clinical Oncology) [9970, 9127]
- FPRC (Fondazione Piemontese per la Ricerca sul Cancro)
- Regione Piemonte (e-LAB project)
- Ministero della Salute
- Ministero dell'Istruzione, dell'Universita e della Ricerca, MIUR FIRB (Fondo per gli Investimenti della Ricerca di Base)-Futuro in Ricerca
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.
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