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高甲硫氨酰-tRNA合成酶表达预示乳腺癌患者预后不良。

High methionyl-tRNA synthetase expression predicts poor prognosis in patients with breast cancer.

作者信息

Jin Qin, Liu Gang, Wang Biao, Li Shubin, Ni Kan, Wang Chunyu, Ren Jingyu, Zhang Shu, Dai Yanfeng

机构信息

Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China.

College of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia, China.

出版信息

J Clin Pathol. 2020 Dec;73(12):803-812. doi: 10.1136/jclinpath-2019-206175. Epub 2020 May 13.

Abstract

AIMS

Methionyl-tRNA synthetase (MARS) is known to play a critical role in initiating translation and protection against cellular damages in vivo. The aim of this study was to clarify the role of MARS in breast cancer (BC) progression.

METHODS

The expressions of messenger RNA (mRNA) and protein in human BC tissues and adjacent non-cancerous tissues were detected by quantitative real-time PCR, western blot and immunohistochemistry. The prognostic potential of MARS in patients with BC was assessed by univariate and multivariate survival analyses. The association between the MARS expression and BC progression was further evaluated by the bioinformatics database of UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Database of Normal and Tumor Tissues (GENT). The role of MARS in the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of human breast cancer cell line (MCF-7 cells) was investigated after siRNA transfection.

RESULTS

The expression level of mRNA in the fresh BC tissues was significantly higher than that in the adjacent tissues. Immunohistochemistry showed that the expression level of MARS was closely associated with the clinicopathologial parameters of patients with BC, including the HER-2 status, Ki-67 status, molecular classification, tumour grade, N stage and tumour, node, metastasis (TNM) stage, and this finding was further confirmed by UALCAN database. The Kaplan-Meier analysis showed that high MARS expression and TNM stage were predictors of poor prognosis of patients with BC. The proliferation, migration and EMT capabilities of MCF-7 cells were significantly suppressed after knockdown. An overview of UALCAN, GEPIA and GENT results suggested that may be an oncogene of BC, as well as a potential therapeutic target of this malignant tumour.

CONCLUSIONS

High expression level of MARS in the human BC tissues was significantly associated with the unfavourable prognosis of patients with BC, suggesting that MARS may serve as a potential prognostic marker for the clinical diagnosis and prognostic prediction of BC.

摘要

目的

已知甲硫氨酰 - tRNA合成酶(MARS)在体内启动翻译和抵御细胞损伤中起关键作用。本研究旨在阐明MARS在乳腺癌(BC)进展中的作用。

方法

通过定量实时PCR、蛋白质印迹法和免疫组织化学检测人BC组织及相邻非癌组织中信使核糖核酸(mRNA)和蛋白质的表达。通过单因素和多因素生存分析评估MARS在BC患者中的预后潜力。通过UALCAN生物信息学数据库、基因表达谱交互式分析(GEPIA)和正常与肿瘤组织基因表达数据库(GENT)进一步评估MARS表达与BC进展之间的关联。在小干扰RNA(siRNA)转染后,研究MARS在人乳腺癌细胞系(MCF - 7细胞)增殖、迁移和上皮 - 间充质转化(EMT)中的作用。

结果

新鲜BC组织中mRNA表达水平显著高于相邻组织。免疫组织化学显示,MARS表达水平与BC患者的临床病理参数密切相关,包括HER - 2状态、Ki - 67状态、分子分类、肿瘤分级、N分期和肿瘤、淋巴结、转移(TNM)分期,UALCAN数据库进一步证实了这一发现。Kaplan - Meier分析表明,高MARS表达和TNM分期是BC患者预后不良的预测指标。敲低后,MCF - 7细胞的增殖、迁移和EMT能力显著受到抑制。UALCAN、GEPIA和GENT结果概述表明,MARS可能是BC的一个癌基因,也是这种恶性肿瘤的潜在治疗靶点。

结论

人BC组织中MARS高表达与BC患者不良预后显著相关,提示MARS可能作为BC临床诊断和预后预测的潜在预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2128/7691814/a8c9ce9cd2f2/jclinpath-2019-206175f01.jpg

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