hERG1 positivity and Glut-1 negativity identifies high-risk TNM stage I and II colorectal cancer patients, regardless of adjuvant chemotherapy.
hERG1 positivity and Glut-1 negativity identifies high-risk TNM stage I and II colorectal cancer patients, regardless of adjuvant chemotherapy.
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DOI：
10.2147/ott.s114090
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发表时间：
2016
影响因子：
4
通讯作者：
Arcangeli A
中科院分区：
文献类型：
--
作者：
Muratori L;Petroni G;Antonuzzo L;Boni L;Iorio J;Lastraioli E;Bartoli G;Messerini L;Di Costanzo F;Arcangeli A
具有高进展风险的早期结直肠癌（CRC）的鉴定是一个主要的临床挑战，主要是由于缺乏经验证的生物标志物。本研究的目的是分析离子通道和转运蛋白家族的三个分子标记物：醚-à-go-go-相关基因1（hERG 1）和钙激活的KCa 3.1钾通道，以及葡萄糖转运蛋白1（Glut-1）;并确定辅助化疗联合上述生物标志物对根治性切除的I-III期CRC患者的影响。采用免疫组织化学方法检测162例非转移性、I-III期结直肠癌患者手术标本中hERG 1、KCa 3.1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，研究生物学标志物、临床病理学特征和生存结局之间的关系。虽然KCa 3.1没有出现预后效价，但提供了hERG 1表达对生存结局产生负面影响的证据。相反，Glut-1的表达有积极的影响。根据多因素分析的结果，将患者分为四个风险组，基于TNM分期和hERG 1/Glut-1表达。调整辅助治疗后，I期和II期、Glut-1阴性和hERG 1阳性患者的生存率最差。这项研究有力地表明，hERG 1阳性和Glut-1阴性的组合表现为根治性切除CRC患者的预后生物标志物。这种组合确定了一组预后不良的I期和II期CRC患者，甚至比III期患者更差，无论辅助治疗是否完成。
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. 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.