Muratori Leonardo, Petroni Giulia, Antonuzzo Lorenzo, Boni Luca, Iorio Jessica, Lastraioli Elena, Bartoli Gianluca, Messerini Luca, Di Costanzo Francesco, Arcangeli Annarosa
Department of Experimental and Clinical Medicine, University of Florence.
Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence; Department of Medical Biotechnologies, University of Siena, Siena.
Onco Targets Ther. 2016 Oct 14;9:6325-6332. doi: 10.2147/OTT.S114090. eCollection 2016.
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 (hERG1) and the KCa3.1 potassium channels, as well as the (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.
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.
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.
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.
识别具有高进展风险的早期结直肠癌（CRC）是一项重大临床挑战，主要原因是缺乏经过验证的生物标志物。本研究的目的是分析属于离子通道和转运蛋白家族的三种分子标志物的预后影响：人乙醚 - 去极化激活钾离子通道1（hERG1）和钙激活钾通道3.1（KCa3.1）以及葡萄糖转运蛋白1（Glut - 1）；并确定在一组接受根治性切除的I - III期CRC患者中，辅助化疗与上述生物标志物联合使用的影响。
通过免疫组织化学检测162例非转移性I - III期CRC患者手术样本中hERG1、KCa3.1和Glut - 1的表达。中位随访时间为32个月。通过评估无病生存期和总生存期，研究生物标志物、临床病理特征和生存结果之间的关联。
虽然KCa3.1未显示出预后价值，但有证据表明hERG1表达对生存结果有负面影响。相反，Glut - 1表达有积极影响。根据多变量分析结果，基于TNM分期和hERG1/Glut - 1表达将患者分为四个风险组。在对辅助治疗进行调整后，I期和II期、Glut - 1阴性且hERG1阳性的患者生存情况最差。
本研究强烈表明，hERG1阳性和Glut - 1阴性的组合在根治性切除的CRC患者中可作为一种预后生物标志物。这种组合识别出一组I期和II期CRC患者，其预后不良，甚至比III期患者更差，无论是否完成辅助治疗。
