GLUT1 and ASCT2 as Predictors for Prognosis of Hepatocellular Carcinoma

PLoS One. 2016 Dec 30;11(12):e0168907. doi: 10.1371/journal.pone.0168907. eCollection 2016.

Abstract

An emerging hallmark of cancer is reprogrammed cellular metabolism, and several cancers involve increased glucose intake and glutamine addiction. Hepatocellular carcinoma (HCC) is one of the most fatal cancers, and its molecular basis needs to be delineated to identify biomarkers for its potential treatment without resection. Therefore, this study aimed to determine the metabolism status of HCC by evaluating the expression of the glucose transporter GLUT1 and glutamine transporter ASCT2. We enrolled 192 patients with surgically resected HCC in this study. Their tissue samples were subjected to immunohistochemistry to detect GLUT1 and ASCT2 expression. The prognostic value of GLUT1 and ASCT2 expression and their combined metabolic index was determined by Kaplan-Meier analysis and the Cox proportional hazards model. We found that GLUT1 and ASCT2 expression was significantly upregulated in tumor tissues as compared to adjacent non-tumor tissues and was positively associated with tumor size. Survival analysis revealed that patients with high GLUT1 or ASCT2 expression had poor overall survival (OS) and recurrence-free survival (RFS). In HCC patients, ASCT2 expression was an independent negative prognostic factor for OS (hazard ratio [HR], 1.760; 95% confidence interval [CI] = 1.124-2.755; p = 0.013) and the metabolic index was an independent negative prognostic factor for OS (HR = 1.672, 95% CI = 1.275-2.193, p < 0.001) and RFS (HR = 1.362, 95% CI = 1.066-1.740, p = 0.013). In conclusion, the tumor metabolism status determined by expression of GLUT1 and ASCT2 and their metabolic index is a promising prognostic predictor for HCC patients.

MeSH terms

  • Adult
  • Aged
  • Amino Acid Transport System ASC / metabolism*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Disease-Free Survival
  • Female
  • Glucose Transporter Type 1 / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens / metabolism*
  • Prognosis
  • Proportional Hazards Models
  • Survival Analysis
  • Young Adult

Substances

  • Amino Acid Transport System ASC
  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • Minor Histocompatibility Antigens
  • SLC1A5 protein, human
  • SLC2A1 protein, human

Grants and funding

This work was supported by grants from National Natural Science Foundation of China (JX, No.81301793; W-CW, No.81502455) and Health Medical Collaborative Innovation Program of Guangzhou (LZ, No. 201400000001-3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.