Prognosis-related miRNA bioinformatics screening of lung adenocarcinoma and its clinical significance

doi:10.12047/j.cjap.5755.2018.118

Abstract

Abstract: Objective: To investigate the prognosis-related miRNA histological features and clinical significance of lung adenocarcinoma. Methods: Using The Cancer Genome Atlas (TCGA) data, the miRNA expression profile data of human lung adenocarcinoma were searched for differential analysis, and the prognosis-related miRNAs were screened by Cox risk regression model. The targeted miRNAs were predicted by mirwalk analysis platform, KEGG functional enrichment analysis, and finally, predict the function of prognosis-related miRNAs. Results: A total of 46 differential miRNAs in lung adenocarcinoma were screened, including 19 up-regulated and 27 down-regulated. Six prognostic-related miRNAs were screened by Cox survival analysis, namely hsa-mir-21, hsa-mir-142, hsa-mir-200a high expression, hsa-mir-101, hsa-let-7c, hsa-mir-378e low expression, hsa-mir-21 and hsa-mir-378e were associated with poor prognosis in patients with lung adenocarcinoma, and the survival time was shortened significantly (P<0.05, AUC=0.618). KEGG analysis showed that the above prognosis-related miRNA targeting regulatory genes were related with immune response pathways, miRNA and cancer pathways, metabolic pathways and so on. Conclusion: Hsa-mir-21 and hsa-mir-378e are associated with poor prognosis of lung adenocarcinoma, and may be used as a molecular marker for prognosis of lung adenocarcinoma after further clinical verification.

Key words: lung adenocarcinoma, miRNA, TCGA, prognosis, bioinformatics

ZHANG Hao-min, YANG Bo, CHEN Hong-fei, CHI Xiao-hua, XI Yi-bo, CHEN Xi-meng, GUO Bin, HE Pei-feng, LU Xue-chun. Prognosis-related miRNA bioinformatics screening of lung adenocarcinoma and its clinical significance[J]. CJAP, 2018, 34(6): 530-535.

References

[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424.
[2] 中国癌症研究基金会《中国肿瘤临床年鉴》编辑委员会. 中国肿瘤临床年鉴:2016[M]. 北京:中国协和医科大学出版社, 2017.
[3] Nan X, Xie C, Yu X, et al. EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer[J]. Oncotarget, 2017, 8(43):75712-75726.
[4] Zhang M, Wang Q, Ding Y, et al. CUX1-ALK, a novel ALK rearrangement that responds to crizotinib in non-small cell lung cancer[J]. J Thorac Oncol, 2018, 13(11):1792-1797.
[5] Iqbal MA, Arora S, Prakasam G, et al. MicroRNA in lung cancer:role, mechanisms, pathways and therapeutic relevance[J]. Mol Aspects Med, 2018, pii:S0098-2997(18)30065-7.
[6] Leng Q, Wang Y, Jiang F. A direct plasma miRNA assay for early detection and histological classification of lung cancer[J]. Transl Oncol, 2018, 11(4):883-889.
[7] Kim JE, Eom JS, Kim WY, et al. Diagnostic value of microRNAs derived from exosomes in bronchoalveolar lavage fluid of early-stage lung adenocarcinoma:A pilot study[J]. Thorac Cancer, 2018, 9(8):911-915.
[8] Tomczak K, Czerwinska P, Wiznerowicz M. The Cancer Genome Atlas (TCGA):an immeasurable source of knowledge[J]. Contemp Oncol, 2015, 19(1A):A68-77.
[9] Anders S, Huber W. Differential expression analysis for sequence count data[J]. Genome Biol, 2010, 11(10):R106.
[10] Qi X, Yu Y, Ji N, et al. Genetic risk analysis for an individual according to the theory of programmed onset, illustrated by lung and liver cancers[J]. Gene, 2018, 673:107-111.
[11] Dweep H, Gretz N, Sticht C. miRWalk database for miRNA-target interactions[J]. Methods Mol Biol, 2014, 1182:289-305.
[12] Xiong DD, Dang YW, Lin P, et al. A circRNA-miRNA-mRNA network identification for exploring underlying pathogenesis and therapy strategy of hepatocellular carcinoma[J]. J Transl Med, 2018, 16(1):220.
[13] Catalanotto C, Cogoni C, Zardo G. MicroRNA in control of gene expression:an overview of nuclear functions[J]. Int J Mol Sci, 2016, 17(10):E1712.
[14] Riffo-Campos AL, Riquelme I, Brebi-Mieville P. Tools for sequence-based miRNA target prediction:What to choose[J]? Int J Mol Sci, 2016, 17(12):E1987.
[15] Su C, Cheng X, Li Y, et al. MiR-21 improves invasion and migration of drug-resistant lung adenocarcinoma cancer cell and transformation of EMT through targeting HBP1[J]. Cancer Med, 2018, 7(6):2485-2503.
[16] Misono S, Seki N, Mizuno K, et al. Dual strands of the miR-145 duplex (miR-145-5p and miR-145-3p) regulate oncogenes in lung adenocarcinoma pathogenesis[J]. J Hum Genet, 2018, 63(10):1015-1028.
[17] Migliore C, Morando E, Ghiso E, et al. miR-205 mediates adaptive resistance to MET inhibition via ERRFI1 targeting and raised EGFR signaling[J]. EMBO Mol Med, 2018, 10(9):e8746.
[18] 王红磊, 肖奕, 武力, 等. miR-449a对人乳腺癌细胞MCF-7增殖及迁移能力的影响[J]. 中国应用生理学杂志, 2017, 33(6):508-513.
[19] 陈育娟, 吴培阳, 高瑞秋. MiR-218对滋养层细胞迁移侵袭的影响及其机制研究[J]. 中国应用生理学杂志, 2017, 33(2):169-173.
[20] Yuan Y, Xu XY, Zheng HG, et al. Elevated miR-21 is associated with poor prognosis in non-small cell lung cancer:a systematic review and meta-analysis[J]. Eur Rev Med Pharmacol Sci, 2018, 22(13):4166-4180.
[21] Kunita A, Morita S, Irisa TU, et al. MicroRNA-21 in cancer-associated fibroblasts supports lung adenocarcinoma progression[J]. Sci Rep, 2018, 8(1):8838.
[22] 张楹怡, 田卫平, 梅玫. miR-21与DNA甲基化在不同乳腺癌细胞中的相互作用[J]. 中国应用生理学杂志, 2015, 31(3):220-224.
[23] Kaduthanam S, Gade S, Meister M, et al. Serum miR-142-3p is associated with early relapse in operable lung adenocarcinoma patients[J]. Lung Cancer, 2013, 80(2):223-227.
[24] Lin K, Xu T, He BS, et al. MicroRNA expression profiles predict progression and clinical outcome in lung adenocarcinoma[J]. Onco Targets Ther, 2016, 9:5679-5692.
[25] Yang L, Luo P, Song Q, et al. DNMT1/miR-200a/GOLM1 signaling pathway regulates lung adenocarcinoma cells proliferation[J]. Biomed Pharmacother, 2018, 99:839-847.
[26] Li X, Shi Y, Yin Z, et al. An eight-miRNA signature as a potential biomarker for predicting survival in lung adenocarcinoma[J]. J Transl Med, 2014, 12:159.
[27] Cui SY, Huang JY, Chen YT, et al. Let-7c governs the acquisition of chemo-or radioresistance and epithelial-to-mesenchymal transition phenotypes in docetaxel-resistant lung adenocarcinoma[J]. Mol Cancer Res, 2013, 11(7):699-713.
[28] Kurimoto R, Iwasawa S, Ebata T, et al. Drug resistance originating from a TGF-β/FGF-2-driven epithelial-to-mesenchymal transition and its reversion in human lung adenocarcinoma cell lines harboring an EGFR mutation[J]. Int J Oncol, 2016, 48(5):1825-1836.
[29] Ho CS, Noor SM, Nagoor NH. MiR-378 and MiR-1827 regulate tumor invasion, migration and angiogenesis in human lung adenocarcinoma by targeting RBX1 and CRKL, respectively[J]. J Cancer, 2018, 9(2):331-345.
[30] Martínez-Terroba E, Behrens C, de Miguel FJ, et al. A novel protein-based prognostic signature improves risk stratification to guide clinical management in early-stage lung adenocarcinoma patients[J]. J Pathol, 2018, 245(4):421-432.