title: GLUT1 and ASCT2 as Predictors for Prognosis of Hepatocellular Carcinoma.
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.
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Sun
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Xing-Juan
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Wu
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|School of Life Science, Sun Yat-sen University, Guangzhou, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|School of Life Science, Sun Yat-sen University, Guangzhou, P. R. China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D026962:Amino Acid Transport System ASC / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D026962:Amino Acid Transport System ASC; D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; D015778:Minor Histocompatibility Antigens; C420506:SLC1A5 protein, human; C495677:SLC2A1 protein, human