Monocarboxylate Transporter 4 (MCT4) Overexpression Is Correlated with Poor Prognosis of Osteosarcoma

Abstract

Background Monocarboxylate transporter 4 (MCT4) is a critical element for glycolytic metabolism and malignant behaviors in many tumor cells. This study aimed to determine the expression level of MCT4 protein and its prognostic value in osteosarcoma. Material/Methods MCT4 expression was detected via immunohistochemical and Western blot analysis for 100 osteosarcoma patients. The correlation between MCT4 expression and clinical factors among the patients was analyzed using the chi-square test. Overall survival of osteosarcoma patients was estimated by Kaplan-Meier analysis. The prognostic value of MCT4 was evaluated using Cox regression analysis with adjustments for clinicopathological variables. Results MCT4 expression was significantly upregulated in osteosarcoma tissues compared with that in adjacent normal ones, detected via both immunohistochemical and Western blot analyses. High MCT4 expression showed a positive association with distant metastasis ( P =0.000) and recurrence ( P =0.000) of osteosarcoma. Kaplan-Meier analysis indicated that overall survival of osteosarcoma patients was significantly higher in the low MCT4 expression group than in the high expression group (log-rank test, P <0.001). Multivariate analysis indicated that MCT4 expression and clinical stage, which are tightly related to the prognosis of osteosarcoma, might be independent predictors of osteosarcoma prognosis. Conclusions High MCT4 expression appears to contribute to osteosarcoma progression and the upregulation of MCT4 may predict poor prognosis among osteosarcoma patients.

High expression of monocarboxylate transporter 4 (MCT 4), but not MCT 1, predicts poor prognosis in patients with non-small cell lung cancer

“…The monocarboxylate transporter (MCT) family, especially MCT1 and MCT4, have been recognized as important lactate transporters. Also, the over-expression of MCT1 and MCT4 has been observed in various cancers ( 7 - 9 ) including esophageal squamous cell carcinoma ( 10 ), glioblastoma ( 11 ) and breast cancer ( 12 , 13 ), osteosarcoma ( 14 ), hepatocellular carcinoma ( 15 , 16 ), oral squamous cell carcinoma ( 17 ), prostate cancer ( 18 ), and lung adenocarcinoma ( 19 ), and has also been associated with survival outcomes. In urothelial carcinoma, increased MCT4 levels, either ribonucleic acid (RNA) or protein, is a predictor of worse overall survival (OS).…”

Construction of a competing endogenous RNA network related to the prognosis of cholangiocarcinoma and comprehensive analysis of the immunological correlation

“…SLC16A3, also known as MCT4, is a member of the monocarboxylic acid transporter (MCT) family. It has been found to be highly expressed in a variety of malignant tumor tissues, such as renal cell renal carcinoma, hepatocellular carcinoma, osteosarcoma, and is associated with patient prognosis (25)(26)(27). DDX4 is an ATP-dependent RNA helicase belonging to the DEAD box protein family, and is also expressed by spermatogonial progenitors.…”

Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies

“…The overexpression of several additional metabolic genes has also been correlated with poor survival in osteosarcoma, including X-Box Binding Protein 1 (XBP1), monocarboxylate transporter 4 (MCT4), and 3-phosphoglycerate dehydrogenase (PHGDH) [ 37 , 115 , 116 ]. Targeting these tumor biomarkers by inhibiting the overexpressed metabolic genes typically results in decreased proliferation and cytostasis, but the innate adaptability of metabolic pathways leads to limited clinical applicability of metabolic inhibitors as single agents [ 117 , 118 ].…”