基于异常糖代谢探讨MCT4参与胃癌发生发展的机制

Exploring the mechanism of MCT 4 involved in the development of gastric cancer based on abnormal glucose metabolism

目的探讨单羧酸转运蛋白(MCT)在胃癌的表达及临床意义。方法选取2018年1月—2020年12月徐州市中心医院收治的病理学诊断为胃腺癌的患者56例。收集其胃癌组织及其配对的癌旁正常组织标本、正电子发射计算机断层成像(PET/CT)结果。采用GEPIA2和kmplot数据库分析MCT1-4在胃癌组织的表达及其与胃癌疾病分期和预后的相关性。采用免疫组化法检测MCT4、葡萄糖转运蛋白(GLUT1)及缺氧诱导因子(HIF)-1α的表达。采用GEPIA2在线分析MCT4表达与GLUT1和HIF-1的关系。结果GEPIA2分析显示,MCT1和MCT4基因表达在胃癌组织较非肿瘤组织显著增高(P<0.05),而MCT2和MCT3的基因表达差异无统计学意义(P>0.05);MCT1和MCT4基因与胃癌分期相关性差异无统计学意义(P>0.05)。kmplot数据库显示MCT1 mRNA高表达患者总生存期(OS)增加(P<0.001),MCT4 mRNA高表达患者OS减少(P<0.001)。此外,MCT4蛋白表达在胃癌组织较正常组织明显升高(P=0.0006)。GEPIA2分析和免疫组化染色结果提示MCT4表达与葡萄糖转运蛋白(GLUT1)和缺氧诱导因子(HIF-1)的表达呈正相关。结论MCT4参与调控GC糖代谢的重编程和肿瘤微环境,与GC的发生发展密切相关,可作为潜在的预后标志物,有可能作为GC患者的候选治疗靶点。

Objective To investigate the expression of monocarboxylate transporter proteins(MCTs)in gastric cancer tissues and its clinical significance.Methods A total of 56 patients who were admitted to Xuzhou Central Hospital from January 2018 to December 2020 and pathologically diagnosed with gastric cancer were selected.Their gastric cancer tissues and adjacent normal tissues,as well as positron emission tomography/computedtomography(PET/CT)results were collected.The GEPIA2 and kmplot databases were adopted to analyze the expression of MCT1-4 in gastric tissues and its relation with disease classification and prognosis.The expression of MCT4,glucose transporter 1(GLUT1)and hypoxia inducible factor-1α(HIF-1α)was detected by immunohistochemistry.The relationship between MCT4 expression and GLUT1 and HIF-1α were analyzed by GEPIA1 database.Results According to GEPIA1 online analysis,the levels of MCT1 and MCT4 mRNA were significantly higher in gastric cancer tissues,compared with those in the non-gastric cancer tissues(P<0.05).No statistical difference was found MCT2 and MCT3 expression(P>0.05).There was no relationship between MCT1 and MCT4 gene and the classification of gastric cancer(P>0.05).According to kmplot database,gastric cancer patients with high MCT1 mRNA expression presented increased overall survival(OS)(P<0.001),while those with high MCT4 mRNA expression had decreased OS(P<0.001).Furthermore,MCT4 protein levels were significantly elevated in gastric cancer tissues compared with adjacent normal tissues(P=0.0006).GEPIA2 analysis and immunohistochemical results indicated that MCT4 expression was positively correlated with GLUT1 and HIF-1αprotein.Conclusions MCT4 is involved in regulating the reprogramming of GC glucose metabolism and tumor microenvironment,which is closely related to the occurrence and development of GC and can be used as a potential prognostic marker.