Glucose Transporter 1 (SLC2A1) and Vascular Endothelial Growth Factor A (VEGFA) Predict Survival After Resection of Colorectal Cancer Liver Metastasis
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Publication date
2016-01
Authors
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, G A
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Article
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taverne
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.
Keywords
Colorectal Neoplasms, Glucose Transporter Type 1, VEGFA, Hypoxia-Inducible Factor 1, alpha Subunit, Liver Neoplasms, prognostic biomarker, SLC2A1, Survival Rate, Vascular Endothelial Growth Factor A, colorectal cancer, HIF1, liver metastasis, Taverne, Journal Article, Research Support, Non-U.S. Gov't
Citation
Goos, J A C M, de Cuba, E M V, Coupé, V M H, Diosdado, B, Delis-Van Diemen, P M, Karga, C, Beliën, J A M, Menke-Van der Houven van Oordt, C W, Geldof, A A, Meijer, G A, Hoekstra, O S, Fijneman, R J A, DeCoDe PET Group, Lam, MGEH, Borel Rinkes, IHM, van Diest, PJ, van Hillegersberg, R & Kranenburg, OW 2016, 'Glucose Transporter 1 (SLC2A1) and Vascular Endothelial Growth Factor A (VEGFA) Predict Survival After Resection of Colorectal Cancer Liver Metastasis', Annals of Surgery, vol. 263, no. 1, pp. 138-145. https://doi.org/10.1097/SLA.0000000000001109