1. Glucose Transporter 1 (SLC2A1) and Vascular Endothelial Growth Factor A (VEGFA) Predict Survival After Resection of Colorectal Cancer Liver Metastasis
- Author
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Goos, Jeroen A C M, de Cuba, Erienne M V, Coupé, Veerle M H, Diosdado, Begoña, Delis-Van Diemen, Pien M, Karga, Cemile, Beliën, Jeroen A M, Menke-Van der Houven van Oordt, C Willemien, Geldof, Albert A, Meijer, Gerrit A, Hoekstra, Otto S, Fijneman, Remond J A, DeCoDe PET Group, Lam, MGEH, Borel Rinkes, IHM, van Diest, PJ, van Hillegersberg, R, and Kranenburg, OW
- Subjects
VEGFA ,Vascular Endothelial Growth Factor A ,Glucose Transporter Type 1 ,Research Support, Non-U.S. Gov't ,Liver Neoplasms ,SLC2A1 ,HIF1 ,colorectal cancer ,Hypoxia-Inducible Factor 1, alpha Subunit ,Survival Rate ,liver metastasis ,Journal Article ,Colorectal Neoplasms ,prognostic biomarker - Abstract
OBJECTIVE: To investigate the individual and combined prognostic value of HIF1α, SLC2A1, and vascular endothelial growth factor A (VEGFA) in a multi-institutional cohort of patients with resected colorectal cancer liver metastasis (CRCLM). BACKGROUND: In the majority of patients with CRCLM, resection seems not to be curative, despite its curative intent. Overexpression of hypoxia-inducible factor 1α (HIF1α), glucose transporter 1 (SLC2A1; also known as GLUT1), and VEGFA has been associated with tumor progression and poor prognosis of patients with colorectal cancer (CRC). METHODS: Tissue microarrays were generated using CRCLM and patient-matched primary CRC from patients who underwent CRCLM resection between 1990 and 2010. Prognostic value of HIF1α, SLC2A1, and VEGFA was determined by immunohistochemistry. A 500-fold cross-validated hazard rate ratio (HRRav) for overall survival was calculated. RESULTS: HIF1α, SLC2A1, and VEGFA expression could be evaluated in 328, 350, and 335 patients, respectively. High SLC2A1 expression was associated with good prognosis (HRRav, 0.67; P (HRR >1) < 0.01) and high VEGFA expression to poor prognosis (HRRav, 1.84; P (HRR < 1) = 0.02), also after multivariate analysis including established clinicopathological prognostic variables (HRRav, 0.67; P (HRR > 1) < 0.01 and HRRav, 1.50; P (HRR < 1) = 0.02, respectively). SLC2A1 showed prognostic value particularly in patients treated with systemic therapy (P < 0.01), whereas the prognostic value of VEGFA expression was mainly observed in patients not treated with systemic therapy (P < 0.01). Prognosis was especially poor in patients with both low SLC2A1 and high VEGFA expression (P < 0.01). HIF1α expression was not associated with survival. CONCLUSIONS: SLC2A1 and VEGFA expression are prognostic molecular biomarkers for patients with CRCLM with added value to established clinicopathological variables.
- Published
- 2016