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通过生物信息学和荟萃分析确定LncRNA NEAT1-miR-101-3p/miR-335-5p/miR-374a-3p/miR-628-5p-TRIM6轴为肺腺癌的预后生物标志物。

LncRNA NEAT1-miR-101-3p/miR-335-5p/miR-374a-3p/miR-628-5p-TRIM6 axis identified as the prognostic biomarker for lung adenocarcinoma via bioinformatics and meta-analysis.

作者信息

Ding Dong-Xiao, Li Qiao, Shi Ke, Li Hui, Guo Qiang, Zhang Yun-Qiang

机构信息

Department of Thoracic Surgery, Beilun District People's Hospital of Ningbo, Ningbo, China.

Department of Thoracic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.

出版信息

Transl Cancer Res. 2021 Nov;10(11):4870-4883. doi: 10.21037/tcr-21-2181.

Abstract

BACKGROUND

Overexpression of the tripartite motif containing 6 (TRIM6) is associated with dismal prognosis in cancer patients, but its exact roles in lung adenocarcinoma (LUAD) have not been reported.

METHODS

The roles of TRIM6 are identified by using The Cancer Genome Atlas (TCGA), TIMER2, Gene Expression Omnibus (GEO), etc., and the regulatory networks and related-prognostic biomarkers of TRIM6 are identified via the ENCORI and LNCAR databases in the LUAD progression.

RESULTS

TRIM6 expression level in LUAD tissues was significantly increased. TRIM6 over-expression level in LUAD patients was associated with smoking, clinical stage, histological type, lymph node metastasis, TP53 mutation and dismal prognosis, and related to prognosis-related age, race, sex, clinical stage and tumor purity of LUAD patients. TRIM6 overexpression was associated with the levels of CD8 T cells, macrophages, neutrophils and myeloid dendritic cells, and correlated with the levels of LUAD immune cell markers CD8A, IRF5, CD163, VSIG4, MS4A4A, ITGAM, HLA-DPA1, NRP1, ITGAX, etc. TRIM6 might influence the progression of LUAD by regulating homologous recombination, oocyte meiosis, and ubiquitin-mediated proteolysis. LUAD patients with overexpression of miR-101-3p, miR-335-5p, miR-374a-3p, miR-628-5p, and NEAT1 had a poor prognosis.

CONCLUSIONS

NEAT1-miR-101-3p/335-5p/374a-3p/628-5p-TRIM6 network, which we constructed from our results, might be an important factor in the dismal prognosis of LUAD patients.

摘要

背景

含三联基序蛋白6(TRIM6)的过表达与癌症患者的不良预后相关,但其在肺腺癌(LUAD)中的具体作用尚未见报道。

方法

利用癌症基因组图谱(TCGA)、TIMER2、基因表达综合数据库(GEO)等确定TRIM6的作用,并通过ENCORI和LNCAR数据库在LUAD进展过程中确定TRIM6的调控网络及相关预后生物标志物。

结果

LUAD组织中TRIM6表达水平显著升高。LUAD患者中TRIM6的过表达水平与吸烟、临床分期、组织学类型、淋巴结转移、TP53突变及不良预后相关,且与LUAD患者的预后相关年龄、种族、性别、临床分期及肿瘤纯度有关。TRIM6过表达与CD8 T细胞、巨噬细胞、中性粒细胞和髓样树突状细胞水平相关,并与LUAD免疫细胞标志物CD8A、IRF5、CD163、VSIG4、MS4A4A、ITGAM、HLA - DPA1、NRP1、ITGAX等水平相关。TRIM6可能通过调节同源重组、卵母细胞减数分裂和泛素介导的蛋白水解影响LUAD的进展。miR - 101 - 3p、miR - 335 - 5p、miR - 374a - 3p、miR - 628 - 5p和NEAT1过表达 的LUAD患者预后较差。

结论

根据我们的研究结果构建的NEAT1 - miR - 101 - 3p/335 - 5p/374a - 3p/628 - 5p - TRIM6网络可能是LUAD患者不良预后的一个重要因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eb9/8798981/0375dbc47491/tcr-10-11-4870-f1.jpg

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