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Cancer Med. 2018 Nov;7(11):5339-5350. doi: 10.1002/cam4.1521. Epub 2018 Oct 10.

Aberrant MCT4 and GLUT1 expression is correlated with early recurrence and poor prognosis of hepatocellular carcinoma after hepatectomy.

Chen HL1,2,3, OuYang HY4, Le Y1,2,3, Jiang P5, Tang H6, Yu ZS1,2,3, He MK1,2,3, Tang YQ6, Shi M1,2,3.

Author information

1
Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
2
Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, China.
3
Sate Key Laboratory of Oncology in South Guangzhou, 510060, Guangdong, China.
4
GI Cell Biology Research Laboratory, Children's Hospital Boston and Harvard Medical School, Boston, MA, USA.
5
Fourth Internal Medicine, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China.
6
Department of Hepatobiliary Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, 510095, Guangdong, China.

Abstract

The tumor microenvironment is a key determinant of cancer cell biology. The microenvironment is a complex mixture of tumor cells, stromal cells, and proteins, extracellular matrix, oxygen tension, and pH levels surrounding the cells that regulate the tumor progress. This study identified the prognostic factors associated with hepatocellular carcinoma (HCC) and MCT4 and GLUT1 expression levels in HCC specimens. In this study, we analyzed MCT4 and GLUT1 expression levels in tissue samples from 213 patients with HCC by immunohistochemical analyses and in HCC tumor tissues and matched adjacent nonneoplastic tissues by quantitative real-time PCR. We conducted a prognostic analysis of the overall survival (OS) and time to recurrence (TTR) using immunoreactivity and other common clinical and pathological parameters. All variables with prognostic impact were further analyzed by multivariate analysis. We found that MCT4 and GLUT1 expression levels were significantly higher in tumor tissues than in adjacent nontumor tissues, and they were positively correlated with tumor size. Survival analysis showed that patients with high expression levels of MCT4 or GLUT1 had a poor OS and TTR. In patients with HCC, MCT4 expression was an independent negative prognostic factor for OS (hazard ratio [HR] = 1.617; 95% confidence interval [CI] = 1.102-2.374; P = 0.014), and metabolic indicators were independent prognostic factors for OS (HR = 1.617, 95% CI = 1.102-2.374, P = 0.006) and TTR (HR = 1.348, 95% CI = 1.079-1.685, P = 0.009). Interestingly, patients with positive metabolic indicator expression in tumor cells had a significantly shorter OS and earlier TTR than those with negative metabolic indicator expression in tumor cells in the ≤5 cm and >5 cm subgroups. In summary, using the expression of MCT4 and GLUT1 and their metabolic parameters to determine the metabolic status of tumors is promising for predicting the prognosis of patients with HCC.

KEYWORDS:

GLUT1; MCT4; hepatocellular carcinoma; prognosis

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