支链氨基酸氨基转移酶1在乳腺癌中的表达及意义
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摘要
目的探讨乳腺癌中支链氨基酸氨基转移酶1(branched-chain amino acid transferase-1,BCAT1)的表达水平及其预后价值。方法回顾性分析我科2009年至2010年间行乳腺癌根治术的74例乳腺癌标本,通过免疫组织化学的方法检测肿瘤标本及其癌旁正常乳腺组织(20例)中BCAT1的蛋白表达水平,探讨乳腺癌组织中BCAT1的表达情况与临床病理特征及预后的关系。结果免疫组织化学的结果显示,与癌旁正常组织相比,BCAT1在乳腺癌中的表达明显上调(68.9%vs 35.0%,P<0.05)。BCAT1高表达组中进展期T分期、伴淋巴结转移、TNM分期的比例明显高于BCAT1低表达组,而且肿瘤直径较大(分别χ~2=6.228、6.894、7.415、6.210,均P<0.05)。生存分析结果显示BCAT1高表达组和低表达组的5年总体生存率分别为56.9%和82.6%,Log-rank检验提示BCAT1低表达组的术后总体预后明显优于高表达组(χ~2=5.209,P<0.05)。结论乳腺癌组织中BCAT1的蛋白表达上调。BCAT1高表达与肿瘤直径、淋巴转移和预后不佳呈正相关。BCAT1是乳腺癌的潜在生物学靶点。
Objective To investigate the expression level and prognostic value of branchedchain amino acid transferase-1(BCAT1)in breast cancer. Methods We retrospectively analyzed the specimens of 74 patients with breast cancer who underwent radical mastectomy from 2009 to 2010 in our department. Immunohistochemistry assay was carried out to assess the protein expression levels of BCAT1 in breast cancer and the adjacent normal tissue. The relationship between BCAT1 expression and clinical parameters and survival outcome were also studied. Result According to theimmunohistochemistry assay,the expression of BCAT1 protein in breast cancer was significantly higher than that in adjacent normal breast tissues(68.9% vs 35.0%,P<0.05). Moreover,the high BCAT1 group had higher percentages of advanced T stage,lymph node metastasis,advanced TNM stage and larger tumor size compared with the ones in the low BCAT1 group(χ~2=6.228,6.894,7.415,6.210 respectively,all P values <0.05). The overall 5-year survival rate in the high and low BCAT1 group was 56.9% and 82.6% and the log-rank test revealed that the survival outcome in the low BCAT1 group was significantly better than the one in the high BCAT1 group(χ~2=5.209,P<0.05). Conclusion BCAT1 protein expression was elevated in breast cancer. Moreover,the high expression of BCAT1 expression was positively associated with tumor size,lymph node metastasis and survival outcome. BCAT1 may be a potential target of breast cancer.
Objective To investigate the expression level and prognostic value of branchedchain amino acid transferase-1(BCAT1)in breast cancer. Methods We retrospectively analyzed the specimens of 74 patients with breast cancer who underwent radical mastectomy from 2009 to 2010 in our department. Immunohistochemistry assay was carried out to assess the protein expression levels of BCAT1 in breast cancer and the adjacent normal tissue. The relationship between BCAT1 expression and clinical parameters and survival outcome were also studied. Result According to theimmunohistochemistry assay,the expression of BCAT1 protein in breast cancer was significantly higher than that in adjacent normal breast tissues(68.9% vs 35.0%,P<0.05). Moreover,the high BCAT1 group had higher percentages of advanced T stage,lymph node metastasis,advanced TNM stage and larger tumor size compared with the ones in the low BCAT1 group(χ~2=6.228,6.894,7.415,6.210 respectively,all P values <0.05). The overall 5-year survival rate in the high and low BCAT1 group was 56.9% and 82.6% and the log-rank test revealed that the survival outcome in the low BCAT1 group was significantly better than the one in the high BCAT1 group(χ~2=5.209,P<0.05). Conclusion BCAT1 protein expression was elevated in breast cancer. Moreover,the high expression of BCAT1 expression was positively associated with tumor size,lymph node metastasis and survival outcome. BCAT1 may be a potential target of breast cancer.
引文
[1]Li CI,Uribe DJ,Daling JR.Clinical characteristics of different histologic types of breast cancer[J].Br J Cancer,2005,93(9):1046-1052.
[2]赖爱军,谢斌辉.BCAT1促进肿瘤发生发展的研究进展[J].世界华人消化杂志,2017,25(17):1536-1542.
[3]张国滨,张晋,徐恒周,等.支链氨基酸氨基转移酶1在恶性胶质瘤中的表达及意义[J].中华神经外科杂志,2015,31(12):1259-1262.
[4]Zhou W,Feng X,Ren C,et al.Over-expression of BCAT1,a c-Myc target gene,induces cell proliferation,migration and invasion in nasopharyngeal carcinoma[J].Mol Cancer,2013,12:53.
[5]Zheng YH,Hu WJ,Chen BC,et al.BCAT1,a key prognostic predictor of hepatocellular carcinoma,promotes cell proliferation and induces chemoresistance to cisplatin[J].Liver Int,2016,36(12):1836-1847.
[6]郭雄图,陈显国,胡玉萍,等.支链氨基酸转氨酶1高表达预测结直肠癌预后不佳的研究[J].中华普通外科学文献_电子版,2017,11(2):89-92.
[7]Niwa O,Kumazaki T,Tsukiyama T,et al.A c DNA clone overexpressed and amplified in a mouse teratocarcinoma line[J].Nucleic Acids Res,1990,18(22):6709.
[8]Zhang L,Han J.Branched-chain amino acid transaminase 1(BCAT1)promotes the growth of breast cancer cells through improving m TOR-mediated mitochondrial biogenesis and function[J].Biochem Biophys Res Commun,2017,486(2):224-231.
[9]Mayers JR,Wu C,Clish CB,et al.Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development[J].Nat Med,2014,20(10):1193-1198.
[10]T?njes M,Barbus S,Park YJ,et al.BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1[J].Nat Med,2013,19(7):901-908.
[11]Zhang EY,Cristofanilli M,Robertson F,et al.Genome wide proteomics of ERBB2 and EGFR and other oncogenic pathways in inflammatory breast cancer[J].J Proteome Res,2013,12(6):2805-2817.
[12]王宏刚,谢睿,沈鹏,等.BCAT1蛋白在肝癌中的表达及与预后的关系[J].山西医科大学学报,2016,47(6):502-504,561.
[13]Xu M,Liu Q,Jia Y,et al.BCAT1 promotes tumor cell migration and invasion in hepatocellular carcinoma[J].Oncol Lett,2016,12(4):2648-2656.
[2]赖爱军,谢斌辉.BCAT1促进肿瘤发生发展的研究进展[J].世界华人消化杂志,2017,25(17):1536-1542.
[3]张国滨,张晋,徐恒周,等.支链氨基酸氨基转移酶1在恶性胶质瘤中的表达及意义[J].中华神经外科杂志,2015,31(12):1259-1262.
[4]Zhou W,Feng X,Ren C,et al.Over-expression of BCAT1,a c-Myc target gene,induces cell proliferation,migration and invasion in nasopharyngeal carcinoma[J].Mol Cancer,2013,12:53.
[5]Zheng YH,Hu WJ,Chen BC,et al.BCAT1,a key prognostic predictor of hepatocellular carcinoma,promotes cell proliferation and induces chemoresistance to cisplatin[J].Liver Int,2016,36(12):1836-1847.
[6]郭雄图,陈显国,胡玉萍,等.支链氨基酸转氨酶1高表达预测结直肠癌预后不佳的研究[J].中华普通外科学文献_电子版,2017,11(2):89-92.
[7]Niwa O,Kumazaki T,Tsukiyama T,et al.A c DNA clone overexpressed and amplified in a mouse teratocarcinoma line[J].Nucleic Acids Res,1990,18(22):6709.
[8]Zhang L,Han J.Branched-chain amino acid transaminase 1(BCAT1)promotes the growth of breast cancer cells through improving m TOR-mediated mitochondrial biogenesis and function[J].Biochem Biophys Res Commun,2017,486(2):224-231.
[9]Mayers JR,Wu C,Clish CB,et al.Elevation of circulating branched-chain amino acids is an early event in human pancreatic adenocarcinoma development[J].Nat Med,2014,20(10):1193-1198.
[10]T?njes M,Barbus S,Park YJ,et al.BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1[J].Nat Med,2013,19(7):901-908.
[11]Zhang EY,Cristofanilli M,Robertson F,et al.Genome wide proteomics of ERBB2 and EGFR and other oncogenic pathways in inflammatory breast cancer[J].J Proteome Res,2013,12(6):2805-2817.
[12]王宏刚,谢睿,沈鹏,等.BCAT1蛋白在肝癌中的表达及与预后的关系[J].山西医科大学学报,2016,47(6):502-504,561.
[13]Xu M,Liu Q,Jia Y,et al.BCAT1 promotes tumor cell migration and invasion in hepatocellular carcinoma[J].Oncol Lett,2016,12(4):2648-2656.