hERG1 positivity and Glut-1 negativity identifies high-risk TNM stage I and II colorectal cancer patients, regardless of adjuvant chemotherapy
| Autor: | Giulia Petroni, Annarosa Arcangeli, Lorenzo Antonuzzo, Gianluca Bartoli, Francesco Di Costanzo, Luca Messerini, Luca Boni, Elena Lastraioli, Leonardo Muratori, Jessica Iorio |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Pathology Multivariate analysis Adjuvant chemotherapy Colorectal cancer 03 medical and health sciences 0302 clinical medicine Risk groups Internal medicine medicine Adjuvant therapy Pharmacology (medical) Biomolecular markers Glucose transporter Ion channels Potassium channels Prognostic markers Original Research business.industry ion channels Negativity effect glucose transporter potassium channels medicine.disease biomolecular markers 030104 developmental biology 030220 oncology & carcinogenesis Cohort Immunohistochemistry business prognostic markers |
| Zdroj: | OncoTargets and therapy |
| ISSN: | 1178-6930 |
| DOI: | 10.2147/ott.s114090 |
| Popis: | 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. Video abstract |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|