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

Abstract

<b>Background:</b> Increasing evidence suggests that stromal monocarboxylate transporter 4 (MCT4) and carbonicanhydrase IX (CA IX) may play key roles in tumor development. However, their clinical value remains largelyunexplored in gastric cancer (GC). The present study aimed to determine clinicopathological significance andprognostic values of stromal MCT4 and CA IX in GC. Materials and <br/><b>Methods</b>: Specimens from 143 GC patientswere immunohistochemically stained using polyclonal anti-MCT4 and anti-CA IX antibodies. Expressionwas correlated with patient clinicopathologic characteristics and survival data. <br/><b>Results</b>: High stromal MCT4expression was detected in 72 of 143 (50.3%) GCs and high CA IX in 74 (51.7%). Both high stromal MCT4 andCA IX were correlated with advanced TNM stage (p=0.000; p=0.000). High CA IX expression was positivelyrelated to depth of invasion (p=0.022) and positive lymph nodes (p=0.002) as well. Survival analysis indicatedhigh expression of stromal MCT4 to be an independent factor in predicting poor overall survival (OS) (HR and95%CI=1.962, 1.032-3.729, p=0.040) and disease free survival (DFS) (HR and 95%CI=2.081, 1.158-3.741, p=0.014)of GC patients. However, high CA IX expression exhibited no significant predictive value. <br/><b>Conclusions</b>: Thesefindings suggest that high expression of stromal MCT4 and CA IX proteins is significantly correlated with GCprogression. High stromal MCT4 heralds worse outcome of GC patient, suggesting a novel candidate prognosticmarker and therapeutic target.