Aberrant expression of monocarboxylate transporter 4 in tumour cells predicts an unfavourable outcome in patients with hepatocellular carcinoma

Ohno, Akinobu; Yorita, Kenji; Haruyama, Yukihiro; Kondo, Kazuhiro; Kato, Atsuhiko; Ohtomo, Toshihiko; Kawaguchi, Makiko; Marutuska, Kousuke; Chijiiwa, Kazuo; Kataoka, Hiroaki

doi:10.1111/liv.12466

Cited by 31 publications

(47 citation statements)

References 28 publications

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“…According to data acquired from the TCGA database, MCT4 is expressed at higher levels in ESCC cancerous tissue compared with normal tissue. It is possible that MCT4 may act as an oncogene in ESCC, as it does in other types of cancer (11,12,(14)(15)(16)(17)(18)(19) and it could be a potential prognostic factor for ESCC. Analysis of the associations between patient clinicopathological characteristics and MCT4 expression revealed that MCT4 expression was significantly associated with T stage, N stage and TNM stage.…”

Section: Discussionmentioning

confidence: 99%

“…Expression of MCT4 in cancer or stromal cells in the tumor microenvironment varies among different types of cancer. Overexpression of MCT4 in both epithelial and stromal cells of breast cancer (11)(12)(13), hepatocellular cancer cells (14,15) and pancreatic cancer cells (16) predicted worse outcomes for patients. Furthermore, high expression of MCT4 in stromal cells of colorectal cancer (17), oral squamous cell carcinoma (18) and gastric cancer (19) was revealed to be associated with poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value of monocarboxylate transporter 4 in patients with esophageal squamous cell carcinoma

Cheng

Chen

et al. 2018

Oncol Rep

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Monocarboxylate transporter 4 (MCT4) is a membrane transporter of monocarboxylates that has been reported to play an important role in tumorigenesis and progression in several solid tumor types. The present study aimed to investigate its clinical significance in esophageal squamous cell carcinoma (ESCC). After obtaining and analyzing MCT4 mRNA expression data from The Cancer Genome Atlas (TCGA) database, the prognostic potential of MCT4 was evaluated by IHC analysis. The effect of the knockdown of MCT4 by shRNA was also evaluated using Cell Counting Kit-8 (CCK-8) and clonogenic assays, in order to determine whether MCT4 inhibition affected the proliferation and survival ability of ESCC cells. Flow cytometric analysis was used to evaluate apoptosis. Western blot analysis was performed to detect the expression levels of p-Akt, Bax, Bcl-2, cytoplasmic cytochrome c and cleaved caspase-3. MCT4 expression was associated with T stage (P=0.001), N stage (P=0.020) and formalin‑fixed and paraffin-embedded (TNM) stage (P=0.042). Kaplan-Meier survival analysis indicated that patients in the high-MCT4 group had a lower overall survival (OS) rate (P=0.001) and progression-free survival (PFS) rate (P=0.003). The univariate Cox regression analysis and multivariate Cox regression analysis results indicated that MCT4 is an independent predictor of OS (P=0.001 and 0.014) and PFS (P=0.004 and 0.046). Downregulation of MCT4 inhibited cell proliferation and increased apoptosis in vitro. The proliferation rate and clone numbers were decreased and apoptotic rates were increased in the sh-MCT4 groups (all P<0.05). Furthermore, MCT4 knockdown reduced the activation of Akt and increased Bax/Bcl-2 ratios, cytochrome c release and caspase-3 cleavage (all P<0.05). Consequently, MCT4 could serve as a promising biomarker for ESCC to identify patients with poor prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic value of monocarboxylate transporter 4 in patients with esophageal squamous cell carcinoma

Cheng

Chen

et al. 2018

Oncol Rep

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“…Importantly, these results pointed out MCT4 as a potential marker for tumor aggressiveness, as suggested in other tumor types. [48][49][50][51] Furthermore, the authors suggest that MCT4 may act as a prognosis predictor due to its association with overall survival. 25 In the present study, there was no association between MCT4 and overall survival.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of monocarboxylate transporter expression in oral cavity tumors

et al. 2016

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“…The role of over-expressed MCT4 in HCC has been illustrated. It is associated with HCC progression and poor prognosis[48,49]. The latest study observed the reduced expression of MCT1 and MCT2 in HCC[50].…”

Section: Reprogramming Of Glucose Metabolism-related Enzymes and Tranmentioning

confidence: 99%

Reprogramming of glucose metabolism in hepatocellular carcinoma: Progress and prospects

Shang

Wang

2016

WJG

107

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Hepatocellular carcinoma (HCC) is one of the most lethal cancers, and its rate of incidence is rising annually. Despite the progress in diagnosis and treatment, the overall prognoses of HCC patients remain dismal due to the difficulties in early diagnosis and the high level of tumor invasion, metastasis and recurrence. It is urgent to explore the underlying mechanism of HCC carcinogenesis and progression to find out the specific biomarkers for HCC early diagnosis and the promising target for HCC chemotherapy. Recently, the reprogramming of cancer metabolism has been identified as a hallmark of cancer. The shift from the oxidative phosphorylation metabolic pathway to the glycolysis pathway in HCC meets the demands of rapid cell proliferation and offers a favorable microenvironment for tumor progression. Such metabolic reprogramming could be considered as a critical link between the different HCC genotypes and phenotypes. The regulation of metabolic reprogramming in cancer is complex and may occur via genetic mutations and epigenetic modulations including oncogenes, tumor suppressor genes, signaling pathways, noncoding RNAs, and glycolytic enzymes etc. Understanding the regulatory mechanisms of glycolysis in HCC may enrich our knowledge of hepatocellular carcinogenesis and provide important foundations in the search for novel diagnostic biomarkers and promising therapeutic targets for HCC.

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Aberrant expression of monocarboxylate transporter 4 in tumour cells predicts an unfavourable outcome in patients with hepatocellular carcinoma

Abstract: Aberrant expression of MCT4 in carcinoma cells serves as a novel, independent prognostic factor for HCC, indicating a poorer patient outcome.

Cited by 31 publications

References 28 publications

Prognostic value of monocarboxylate transporter 4 in patients with esophageal squamous cell carcinoma

Prognostic value of monocarboxylate transporter 4 in patients with esophageal squamous cell carcinoma

Prognostic significance of monocarboxylate transporter expression in oral cavity tumors

Reprogramming of glucose metabolism in hepatocellular carcinoma: Progress and prospects

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