OncoTargets and Therapy (Oct 2016)
hERG1 positivity and Glut-1 negativity identifies high-risk TNM stage I and II colorectal cancer patients, regardless of adjuvant chemotherapy
Abstract
Leonardo Muratori,1,* Giulia Petroni,1,* Lorenzo Antonuzzo,2,3 Luca Boni,4 Jessica Iorio,1,3 Elena Lastraioli,1 Gianluca Bartoli,1 Luca Messerini,1 Francesco Di Costanzo,2 Annarosa Arcangeli1 1Department of Experimental and Clinical Medicine, University of Florence, 2Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence, 3Department of Medical Biotechnologies, University of Siena, Siena, 4Clinical Trials Coordinating Center, Istituto Toscano Tumori, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy *These authors contributed equally to this work Background: The identification of early-stage colorectal cancer (CRC) with high risk of progression is one major clinical challenge, mainly due to lack of validated biomarkers. The aims of the present study were to analyze the prognostic impact of three molecular markers belonging to the ion channels and transporters family: the ether-à-go-go-related gene 1 (hERG1) and the calcium-activated KCa3.1 potassium channels, as well as the glucose transporter 1 (Glut-1); and to define the impact of adjuvant chemotherapy in conjunction with the abovementioned biomarkers, in a cohort of radically resected stage I–III CRC patients. Patients and methods: The expressions of hERG1, KCa3.1, and Glut-1 were tested by immunohistochemistry on 162 surgical samples of nonmetastatic, stage I–III CRC patients. The median follow-up was 32 months. The association between biological markers, clinicopathological features, and survival outcomes was investigated by evaluating both disease-free survival and overall survival. Results: Although no prognostic valence emerged for KCa3.1, evidence of a negative impact of hERG1 expression on survival outcomes was provided. On the contrary, Glut-1 expression had a positive impact. According to the results of the multivariate analysis, patients were stratified in four risk groups, based on TNM stage and hERG1/Glut-1 expression. After adjusting for adjuvant therapy, stage I and II, Glut-1-negative, and hERG1-positive patients showed the worst survival experience. Conclusion: This study strongly indicates that the combination of hERG1 positivity and Glut-1 negativity behaves as a prognostic biomarker in radically resected CRC patients. This combination identifies a group of stage I and II CRC patients with a bad prognosis, even worse than that of stage III patients, regardless of adjuvant therapy accomplishment. Keywords: potassium channels, glucose transporter, biomolecular markers, ion channels, prognostic markers
