title: hERG1 positivity and Glut-1 negativity identifies high-risk TNM stage I and II colorectal cancer patients, regardless of adjuvant chemotherapy.
abstract: 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: theether-à-go-go-related gene 1(hERG1) and thecalcium-activatedKCa3.1 potassium channels, as well as theglucose 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Experimental and Clinical Medicine, University of Florence.
authors: Leonardo
authors: L
authors: Muratori
authors: Department of Experimental and Clinical Medicine, University of Florence.
authors: Giulia
authors: G
authors: Petroni
authors: Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence; Department of Medical Biotechnologies, University of Siena, Siena.
authors: Lorenzo
authors: L
authors: Antonuzzo
authors: Clinical Trials Coordinating Center, Istituto Toscano Tumori, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors: Luca
authors: L
authors: Boni
authors: Department of Experimental and Clinical Medicine, University of Florence; Department of Medical Biotechnologies, University of Siena, Siena.
authors: Jessica
authors: J
authors: Iorio
authors: Department of Experimental and Clinical Medicine, University of Florence.
authors: Elena
authors: E
authors: Lastraioli
authors: Department of Experimental and Clinical Medicine, University of Florence.
authors: Gianluca
authors: G
authors: Bartoli
authors: Department of Experimental and Clinical Medicine, University of Florence.
authors: Luca
authors: L
authors: Messerini
authors: Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence.
authors: Francesco
authors: F
authors: Di Costanzo
authors: Department of Experimental and Clinical Medicine, University of Florence.
authors: Annarosa
authors: A
authors: Arcangeli
keywords: biomolecular markers; glucose transporter; ion channels; potassium channels; prognostic markers