Upregulation of SLC2A3 gene and prognosis in colorectal carcinoma: analysis of TCGA data

Eunyoung Kim,Rumi Shin,Seung Chul Heo,Won Seo Park,Kwangsoo Kim,Sohee Jung,Eun Kyung Choe,Jae Hyun Lee,Joon-Hyop Lee,Young Jun Chai

doi:10.1186/s12885-019-5475-x

Abstract

BackgroundUpregulation of SLC2A genes that encode glucose transporter (GLUT) protein is associated with poor prognosis in many cancers. In colorectal cancer, studies reporting the association between overexpression of GLUT and poor clinical outcomes were flawed by small sample sizes or subjective interpretation of immunohistochemical staining. Here, we analyzed mRNA expressions in all 14 SLC2A genes and evaluated the association with prognosis in colorectal cancer using data from the Cancer Genome Atlas (TCGA) database.MethodsIn the present study, we analyzed the expression of SLC2A genes in colorectal cancer and their association with prognosis using data obtained from the TCGA for the discovery sample, and a dataset from the Gene Expression Omnibus for the validation sample.ResultsSLC2A3 was significantly associated with overall survival (OS) and disease-free survival (DFS) in both the discovery sample (345 patients) and validation sample (501 patients). High SLC2A3 expression resulted in shorter OS and DFS. In multivariate analyses, high SLC2A3 levels predicted unfavorable OS (adjusted HR 1.95, 95% CI 1.22–3.11; P = 0.005) and were associated with poor DFS (adjusted HR 1.85, 95% CI 1.10–3.12; P = 0.02). Similar results were found in the discovery set.ConclusionUpregulation of the SLC2A3 genes is associated with decreased OS and DFS in colorectal cancer patients. Therefore, assessment of SLC2A3 gene expression may useful for predicting prognosis in these patients.

Highlights

Upregulation of solute carrier 2A (SLC2A) genes that encode glucose transporter (GLUT) protein is associated with poor prognosis in many cancers
We explored the association between SLC2A1 expression and disease-free survival (DFS) in a multivariate context of Discovery set and Validation set
We found no association between SLC2A1 expression and overall survival (OS) (HR 1.54, 95% Confidence interval (CI): 0.96–2.46; P = 0.07) in rectal cancer patients

Summary

Introduction

Upregulation of SLC2A genes that encode glucose transporter (GLUT) protein is associated with poor prognosis in many cancers. Studies reporting the association between overexpression of GLUT and poor clinical outcomes were flawed by small sample sizes or subjective interpretation of immunohistochemical staining. Most CRCs originate from non-cancerous lesions by one or a combination of three different mechanisms: chromosomal instability, CpG island methylator phenotype, and microsatellite instability [3] Biomarkers of these cytogenetic alterations are of interest for diagnosis, Among the biomarkers, the solute carrier 2A (SLC2A) gene family that encodes glucose transporter (GLUT) proteins has been widely investigated. An association between overexpression of the subtypes of GLUT proteins and poor clinical outcomes has been reported in CRC [9]

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Conclusion