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MACC1 mRNA Levels Predict Cancer Recurrence After Resection of Colorectal Cancer Liver Metastases

Isella, Claudio PhD*,§; Mellano, Alfredo MD; Galimi, Francesco MD; Petti, Consalvo PhD*; Capussotti, Lorenzo MD; De Simone, Michele MD; Bertotti, Andrea MD, PhD‡,§; Medico, Enzo MD, PhD*,§; Muratore, Andrea MD

doi: 10.1097/SLA.0b013e31828f96bc
Original Articles

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.

MACC1 (metastasis associated in colon cancer 1) mRNA expression level is a new easily detectable prognostic biomarker in cancer. In this work, we demonstrated for the first time that MACC1 expression, measured on liver metastasis specimens, is an independent prognostic factor of recurrence after curative resection of colorectal liver metastases.

*Laboratory of Oncogenomics

Department of Surgical Oncology

Laboratory of Molecular Pharmacology, IRC@C: Institute for Cancer Research at Candiolo, Italy

§Department of Oncology, University of Torino

Department of HPB and Digestive Surgery, Mauriziano Hospital, Torino, Italy.

Reprints: Claudio Isella, PhD or Andrea Muratore, MD, IRC@C, Strada Prov. 142, km 3,95—10060 Candiolo (TO) Italy. E-mail: claudio.isella@ircc.it or andrea.muratore@ircc.it.

C.I. and Alfredo M. are the co-first authors, and E.M. and Andrea M. are the co-senior authors.

Disclosure: This work was supported by grants to E.M. from AIRC, FPRC, Regione Piemonte, Ministero della Salute, and to A.B. from MIUR FIRB-Futuro in Ricerca. The authors declare no conflicts of interest.

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© 2013 Lippincott Williams & Wilkins, Inc.