Prognostic significance of monocarboxylate transporter 4 expression in patients with colorectal cancer

Abstract

Abstract. Cancer cells generally have a high rate of glycolysis and produce larger quantities of lactate as compared to the surrounding normal cells. Monocarboxylate transporter 4 (MCT4) is one of the proton pumps exchanging the lactate through the plasma membrane. The prognostic significance of MCT4 expression has not been evaluated in patients with colorectal cancer (CRC). Surgical specimens from 105 CRC patients were immunohistochemically stained using a polyclonal anti-MCT4 antibody. The relationships among the MCT4 expression, clinicopathological factors and prognosis were evaluated. A total of 53 (50.5%) of the 105 patients with CRC were determined to have tumors positive for MCT4 expression. The expression of MCT4 significantly correlated with the tumor size, depth of invasion, lymph node metastasis, distant metastasis and TNM staging. The survival rate of the patients who were positive for MCT4 expression was significantly lower than that of patients with negative MCT4 expression. Positive MCT4 expression was a significantly poor prognostic factor, as determined by both univariate and multivariate analyses. Therefore, positive MCT4 expression appears to be a useful marker for tumor progression and prognosis in patients with CRC.

Overexpression of Reactive Oxygen Species Scavenger Enzymes Is Associated with a Good Prognosis in Triple-Negative Breast Cancer

“…Lactate is exported from stromal cells undergoing aerobic metabolism to adjacent epithelial cancer cells, consistent with the ‘reverse Warburg effect' [37,38]. Two studies suggested that MCT4 overexpression is associated with a poor prognosis in certain cancer types [39,40]. …”

DNA Methylation of the SLC16A3 Promoter Regulates Expression of the Human Lactate Transporter MCT4 in Renal Cancer with Consequences for Clinical Outcome

“…Recent studies identified the monocarboxylate transporter 4 (MCT4) as metabolic target in a variety of tumors (e.g., colon cancer, breast cancer; refs. 7,8). MCT4 (encoded by the SLC16A3 gene) mediates the H þ -coupled transport of monocarboxylates, preferentially lactate, across the plasma membrane.…”

High Monocarboxylate Transporter 4 Protein Expression in Stromal Cells Predicts Adverse Survival in Gastric Cancer

“…In tumor cells, several studies have indicated that the invasion behavior of MCT4 positive cancer cells is stronger than cells not expressing MCT4 (Izumi et al, 2011). It is also proposed that high tumor cells MCT4 expression predicted poor outcomes in several cancers (Pertega-Gomes et al, 2011;Meijer et al, 2012;Nakayama et al, 2012). However, tumors are composed of both tumor and stromal cells, and the latter can comprise over 50% of the tumor mass.…”

“…A number of original studies that investigating clinical and prognostic significances of MCT4 and CA IX level have been conducted in various types of cancers (Chen et al, 2005;Pinheiro et al, 2010;Rademakers et al, 2011;Nakayama et al, 2012;Kim et al, 2014). Nevertheless, clinical values of stromal MCT4 and CA IX in GC remain not entirely clear.…”