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METTL7B(甲基转移酶样7B)被鉴定为肺腺癌的一种新型生物标志物。

METTL7B (methyltransferase-like 7B) identification as a novel biomarker for lung adenocarcinoma.

作者信息

Ali Jawad, Liu Wenwen, Duan Wenzhe, Liu Chang, Song Jing, Ali Sameen, Li Encheng, Wang Qi

机构信息

Department of Respiratory Medicine, The Second Hospital, Dalian Medical University, Dalian, China.

Dalian Medical University, Dalian, China.

出版信息

Ann Transl Med. 2020 Sep;8(18):1130. doi: 10.21037/atm-20-4574.

Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) is still one of the major causes of cancer-related mortality across the globe. Therefore, there is a dire need to identify early specific and sensitive biomarkers or drug targets of LUAD for developing improved diagnosis and clinical management. We aimed to investigate the role of methyltransferase-like 7B (METTL7B) on LUAD tumor development and progression in this study.

METHODS

METTL7B's expression was confirmed in two independent clinical cohort samples, including LUAD tissues microarray (TMA) via immunohistochemistry (IHC) and serum samples via enzyme-linked immunosorbent assay (ELISA). The correlation between METTL7B expression with clinicopathological features and overall survival rate in LUAD patients was then further analyzed. Meanwhile, the messenger ribonucleic acid (mRNA) and protein levels of METTL7B were verified in cell lines and experiments, including cell proliferation assay, and migration. Invasion assays were conducted to explore the effects of METTL7B on LUAD by silencing the protein expression.

RESULTS

METTL7B was remarkably overexpressed in clinical LUAD tumor tissues and serum compared to the normal control group and in LUAD cell lines. The expression level of METTL7B was significantly correlated with tumor size, advanced tumor node and metastases (TNM) stages, and lymph node metastasis. The Kaplan-Meier survival curves proved that high METTL7B expression was significantly associated with a reduced survival rate in LUAD patients (P<0.05), and univariate analysis showed that high METTL7B expression was significantly associated with poor overall survival [hazard ratio (HR) =2.220, 95% confidence interval (CI): 1.211-4.086; P=0.010]. assays showed that METTL7B overexpression augmented cell proliferation, migration, and the invasion in LUAD.

CONCLUSIONS

METTL7B was overexpressed in LUAD and significantly associated with the poor progression, showing that METTL7B may serve as a potential novel biomarker for the diagnosis and prognosis of LUAD. Moreover, METTL7B plays a role in promoting tumor proliferation, migration, and invasion in LUAD.

摘要

背景

肺腺癌(LUAD)仍是全球癌症相关死亡的主要原因之一。因此,迫切需要鉴定LUAD早期的特异性和敏感性生物标志物或药物靶点,以改进诊断和临床管理。在本研究中,我们旨在探讨甲基转移酶样7B(METTL7B)在LUAD肿瘤发生和进展中的作用。

方法

通过免疫组织化学(IHC)在包括LUAD组织芯片(TMA)在内的两个独立临床队列样本中证实METTL7B的表达,并通过酶联免疫吸附测定(ELISA)在血清样本中证实。然后进一步分析METTL7B表达与LUAD患者临床病理特征和总生存率之间的相关性。同时,在细胞系中验证METTL7B的信使核糖核酸(mRNA)和蛋白质水平,并进行包括细胞增殖测定和迁移在内的实验。通过沉默蛋白质表达进行侵袭试验,以探索METTL7B对LUAD的影响。

结果

与正常对照组相比,METTL7B在临床LUAD肿瘤组织、血清以及LUAD细胞系中均显著过表达。METTL7B的表达水平与肿瘤大小、晚期肿瘤淋巴结转移(TNM)分期和淋巴结转移显著相关。Kaplan-Meier生存曲线证明,METTL7B高表达与LUAD患者生存率降低显著相关(P<0.05),单因素分析表明,METTL7B高表达与总体生存不良显著相关[风险比(HR)=2.220,95%置信区间(CI):1.211-4.086;P=0.010]。试验表明,METTL7B过表达增强了LUAD中的细胞增殖、迁移和侵袭。

结论

METTL7B在LUAD中过表达,且与不良进展显著相关,表明METTL7B可能作为LUAD诊断和预后的潜在新型生物标志物。此外,METTL7B在促进LUAD肿瘤增殖、迁移和侵袭中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39f0/7576055/3e5eca11ba6b/atm-08-18-1130-f1.jpg

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