MDM2 binding protein as a predictor of metastasis and a novel prognostic biomarker in patients with gastric cancer

Abstract

MDM2 binding protein (MTBP) has been revealed to be involved in cancer progression and metastasis. However, the role and clinical implication of MTBP expression in gastric cancer (GC) remains poorly understood. The present study aimed to investigate the clinicopathological significance of MTBP and the prognostic determinant in GC. The expression level of MTBP was examined in cancerous and matched adjacent noncancerous gastric mucosa tissues by reverse transcription-quantitative polymerase chain reaction and western blotting. MTBP expression levels were evaluated by immunohistochemical analysis of tissue microarrays for 352 patients, and association between the expression levels and prognosis in patients with GC were investigated. Kaplan-Meier analysis and Cox's regression models were used to investigate the associations between MTBP expression and prognosis of GC patients. The results of the present study revealed decreased MTBP mRNA (P=0.005) and protein (P=0.001) expression levels in tumor tissue compared with in matched adjacent normal tissue mucosa. MTBP expression level in GC was associated with gender (P=0.026), lymph node metastasis (P<0.001), distant metastasis (P=0.026) and pathological tumor-node-metastasis stage (P<0.001). Kaplan-Meier survival analysis demonstrated that patients with high MTBP expression levels exhibited longer survival times compared with patients with low MTBP expression levels. The multivariate logistic regression analysis revealed that MTBP was independently associated with the presence of lymph node [OR, 0.282; 95% confidence interval (CI), 0.161-0.494; P<0.001] and distant metastasis (OR, 0.365; 95% CI, 0.138-0.965; P=0.042). Furthermore, the multivariate Cox analysis revealed that low MTBP expression level was significantly associated with longer overall survival time and was recognized as an independent prognostic factor of patient's survival. MTBP expression level was significantly associated with progression and metastasis in GC, suggesting that MTBP may be used as a predictive marker for patient prognosis of GC.