title: Monocarboxylate transporter 4 predicts poor prognosis in hepatocellular carcinoma and is associated with cell proliferation and migration.
abstract: OBJECTIVE
  Monocarboxylate transporter 4 (MCT4) is a critical component in the glycolytic metabolism of cancer cells, and is also important for malignant behavior. We investigated the expression profile of MCT4, its prognostic value in hepatocellular carcinoma (HCC) patients, its role in HCC cell proliferation and metastasis, and associated initial molecular mechanism.
  
  
  METHODS
  MCT4 expression was examined through immunohistochemical staining of pathological specimens from 318 HCC patients who had undergone hepatectomy. The HCC cell lines were used to validate the relationship between MCT4 expression and cell proliferation, migration, and invasion.
  
  
  RESULTS
  The results show that high MCT4 expression is indicative of elevated alpha fetoprotein levels and larger tumor size, which leads to poorer disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis shows that MCT4 expression is an independent prognostic factor for DFS and OS in HCC patients. In 91 recurrent HCC patients who underwent transarterial chemoembolization (TACE) treatment, low MCT4 expression predicted an effective treatment response and improved OS. Furthermore, in cell line experiments with MCT4 siRNA, cancer cell proliferation, migration, and invasion were closely correlated with the MCT4 expression. Knockdown of MCT4 was associated with down-regulation of phosphorylated AKT and HIF-1α.
  
  
  CONCLUSIONS
  MCT4 expression can predict survival and TACE treatment response for HCC patients. Furthermore, MCT4 plays an important role in HCC cell proliferation, migration, and invasion. The inhibition of MCT4 can induce inactivation of HIF-1α and inhibit phosphorylation of AKT. MCT4 may be a potential therapeutic target for the treatment of HCC.
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.
authors.forename: Heng-Jun
authors.initials: HJ
authors.lastname: Gao
authors.forename: Ming-Chi
authors.initials: MC
authors.lastname: Zhao
authors.forename: Yao-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Guang-Bing
authors.initials: GB
authors.lastname: Li
authors.forename: Min-Shan
authors.initials: MS
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D016461:Chemoembolization, Therapeutic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D011379:Prognosis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; C406962:SLC16A4 protein, human