组织GLUD1表达与乳腺癌分子分型及临床病理学特征的关系

Correlation of GLUD1 expression in tissue and molecular subtype and clinical pathological features in breast cancer

目的 探讨组织谷氨酸脱氢酶1(GLUD1)与乳腺癌分子分型、临床病理学特征的关系。方法 回顾性分析2014年3月—2017年10月期间在联勤保障部队第九八七医院接受乳腺癌手术的145例患者临床资料,采用实时荧光定量PCR法检测组织GLUD1mRNA表达,采用免疫组化法检测组织GLUD1蛋白表达;比较所有患者肿瘤组织中GLUD1mRNA、蛋白表达与乳腺癌分子分型及临床病理学特征之间的相关性。结果 基于美国公共癌症基因数据库(TCGA)中的数据,乳腺癌组织中GLUD1mRNA表达量显著低于正常乳腺组织中的表达量(P<0.05);雌激素受体(ER)阳性组乳腺癌组织中GLUD1mRNA表达量显著高于ER阴性组组织中的表达量(P<0.05);孕激素受体(PR)阳性组乳腺癌组织中GLUD1mRNA表达量显著高于PR阴性组组织中的表达量(P<0.05)。在本研究中,乳腺癌组织中GLUD1mRNA表达量显著低于癌旁乳腺组织(1.00±0.17vs.0.63±0.27,P<0.05),同时肿瘤组织中GLUD1蛋白高表达率显著低于癌旁乳腺组织[28.28%(41/145)vs.53.79%(78/145),P<0.05]。GLUD1蛋白阳性表达组织中GLUD1mRNA表达量高于阴性表达组织(P<0.05)。经Pearson法分析,GLUD1蛋白表达与GLUD1mRNA表达量呈显著正相关性(r=0.735,P<0.001)。乳腺癌组织GLUD1蛋白表达与临床T分期、N分期、肿瘤分级、ER和PR表达状态有关(P<0.05)。在Luminal A型及Luminal B型中GLUD1mRNA和蛋白表达量较其他分子分型高(P<0.05)。结论 乳腺癌患者肿瘤组织中GLUD1mRNA表达量及GLUD1蛋白高表达率均较癌旁组织普遍降低,尤其是多见于恶性化程度更高或ER-/PR-乳腺癌组织中,这有望成为指导乳腺癌个性化治疗的新靶点。

Objective To evaluate the relationship between glutamate dehydrogenase1(GLUD1) in tissue and molecular subtype and clinical pathological features in breast cancer.Methods 145 patients who underwent breast cancer surgery in our hospital from March 2014 to October 2017 were retrospectively analyzed to compare the correlation between GLUD1 protein and GLUD1 mRNA and the molecular subtype and clinical pathological features in breast cancer patients.Results Data from the Cancer Genome Atlas(TCGA) Database showed that the expression level of GLUD1 mRNA in breast cancer tissues was significantly lower than that in normal breast tissues(P<0.05).In addition,the expression level of GLUD1 mRNA in estrogen receptor(ER)+ breast cancer tissue group was significantly higher than that in ER-group(P<0.05).The expression level of GLUD1 mRNA in progesterone receptor(PR)+ breast cancer tissue group was significantly higher than that in PR-group(P<0.05).In this study,the expression level of GLUD1 mRNA in breast cancer tissues was significantly lower than that in paracancerous breast tissues(1.00±0.17vs.0.63±0.27,P<0.05),and the high expression rate of GLUD1 protein in tumor tissues was significantly lower than that in paracancerous breast tissues[28.28%(41/145)vs.53.79%(78/145),P<0.05].In addition,the expression level of GLUD1 mRNA in the tissues with positive expression of GLUD1 protein was higher than that in the tissues with negative expression of GLUD1 protein(P<0.05),and Pearson analysis showed a significant positive correlation between the expression level of GLUD1 protein and GLUD1 mRNA(r=0.735,P<0.001).The expression of GLUD1 protein in breast cancer was related to clinical T stage,N stage,tumor grade,ER and PR expression(P<0.05).The expression level of GLUD1 mRNA was higher in Luminal A and Luminal B than in other molecular subtype(P<0.05).Conclusion The expression level of GLUD1 mRNA and the high expression rate of GLUD1 protein in tumor tissues of breast cancer patients are generally lower than that in paracancerous tissues,especially in breast cancer tissues with higher degree of malignancy or ER-/PR-,which is expected to become a new target to guide personalized treatment of breast cancer.