Wang Wei, Chen Zhong, Jin Jiejie, Long Ziwen, Liu Xiaowen, Cai Hong, Zhou Ye, Huang Hua, Wang Yanong
Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China.
Oncol Lett. 2017 Dec;14(6):6409-6416. doi: 10.3892/ol.2017.7031. Epub 2017 Sep 22.
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.
MDM2结合蛋白(MTBP)已被揭示与癌症进展和转移有关。然而,MTBP表达在胃癌(GC)中的作用和临床意义仍知之甚少。本研究旨在探讨MTBP在GC中的临床病理意义及预后决定因素。通过逆转录定量聚合酶链反应和蛋白质印迹法检测癌组织及配对的相邻非癌胃黏膜组织中MTBP的表达水平。通过对352例患者的组织芯片进行免疫组化分析评估MTBP表达水平,并研究其表达水平与GC患者预后的相关性。采用Kaplan-Meier分析和Cox回归模型研究MTBP表达与GC患者预后的相关性。本研究结果显示,与配对的相邻正常组织黏膜相比,肿瘤组织中MTBP mRNA(P=0.005)和蛋白(P=0.001)表达水平降低。GC中MTBP表达水平与性别(P=0.026)、淋巴结转移(P<0.001)、远处转移(P=0.026)及病理肿瘤-淋巴结-转移分期(P<0.001)相关。Kaplan-Meier生存分析表明,与MTBP表达水平低的患者相比,MTBP表达水平高的患者生存时间更长。多因素逻辑回归分析显示,MTBP与淋巴结转移(比值比[OR],0.282;95%置信区间[CI],0.161-0.494;P<0.001)和远处转移(OR,0.365;95%CI,0.138-0.965;P=0.042)独立相关。此外,多因素Cox分析显示,MTBP低表达水平与更长的总生存时间显著相关,并且被认为是患者生存的独立预后因素。MTBP表达水平与GC的进展和转移显著相关,提示MTBP可能作为GC患者预后的预测标志物。