Open Access

Prognostic value of microRNAs in lung cancer: A systematic review and meta‑analysis

  • Authors:
    • Wendi Xiao
    • Yucheng Zhong
    • Lili Wu
    • Dongxia Yang
    • Songqing Ye
    • Min Zhang
  • View Affiliations

  • Published online on: November 13, 2018     https://doi.org/10.3892/mco.2018.1763
  • Pages: 67-77
  • Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lung cancer is one of the leading causes of cancer‑associated mortality throughout the world. The prognosis of the disease depends on many factors including the stage and type of cancer. Many studies have identified various microRNAs (miRNAs) that affect the prognosis of lung cancer. In order to systemically analyze the available clinical data, the present study performed a meta‑analysis to examine all evidence on the potential role of miRNAs as novel predictors of survival in lung cancer. Literature published in English prior to February 1st, 2018 was searched through PubMed to review all of the associations between individual miRNAs and groups of miRNAs with the prognosis of lung cancer. Data was extracted using standard forms and pooled odds ratios with 95% confidence intervals (CIs) were calculated. A total of 15 eligible studies were included in the meta‑analysis. These represented 1,753 lung cancer patients and 20 miRNAs. A total of 8 downregulated miRNAs were associated with poorer overall survival (OS) [hazard ratio (HR)=0.59, 95% CI: 0.47‑0.75, P<1x10‑4], while 10 upregulated miRNAs were associated with poorer OS (HR=1.76, 95% CI: 1.31‑2.35, P<1x10‑4). Additionally, low miRNA expression was associated with lymph node metastasis [LNM; relative risk (RR)=0.53, 95% CI: 0.46‑0.61, P<1x10‑4]. The expression of miRNAs was not associated with lung cancer stage (RR=1.07, 95% CI: 0.94‑1.22, P=0.23). Expression levels of different miRNAs were associated with the OS and LNM of patients with lung cancer. These miRNAs may be applied as potential prognostic markers in lung cancer.

References

1 

Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Torre LA, Siegel RL and Jemal A: Lung cancer statistics. Adv Exp Med Biol. 893:1–19. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Li D, Song L, Wen Z, Li X, Jie J, Wang Y and Peng L: Strong evidence for LncRNA ZNRD1-AS1, and its functional Cis-eQTL locus contributing more to the susceptibility of lung cancer. Oncotarget. 7:35813–35817. 2016.PubMed/NCBI

5 

Castro D, Moreira M, Gouveia AM, Pozza DH and De Mello RA: microRNAs in lung cancer. Oncotarget. 8:81679–81685. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Aghanoori MR, Mirzaei B and Tavallaei M: miRNA molecular profiles in human medical conditions: Connecting lung cancer and lung development phenomena. Asian Pac J Cancer Prev. 15:9557–9565. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Kozomara A and Griffiths-Jones S: miR base: Annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 42:D68–D73. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Zhong Y, Chen Z, Guo S, Liao X, Xie H, Zheng Y, Cai B, Huang P, Liu Y, Zhou Q, et al: TUG1, SPRY4-IT1, and HULC as valuable prognostic biomarkers of survival in cancer: A PRISMA-compliant meta-analysis. Medicine (Baltimore). 96:e85832017. View Article : Google Scholar : PubMed/NCBI

9 

Kang M, Shi J, Peng N and He S: MicroRNA-211 promotes non-small-cell lung cancer proliferation and invasion by targeting MxA. OncoTargets Ther. 10:5667–5675. 2017. View Article : Google Scholar

10 

Mavridis K, Gueugnon F, Petit-Courty A, Courty Y, Barascu A, Guyetant S and Scorilas A: The oncomiR miR-197 is a novel prognostic indicator for non-small cell lung cancer patients. Br J Cancer. 112:1527–1535. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Wang F, Lou JF, Cao Y, Shi XH, Wang P, Xu J, Xie EF, Xu T, Sun RH, Rao JY, et al: miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy. Exp Mol Med. 47:e1622015. View Article : Google Scholar : PubMed/NCBI

12 

Võsa U, Vooder T, Kolde R, Vilo J, Metspalu A and Annilo T: Meta-analysis of microRNA expression in lung cancer. Int J Cancer. 132:2884–2893. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Guan P, Yin Z, Li X, Wu W and Zhou B: Meta-analysis of human lung cancer microRNA expression profiling studies comparing cancer tissues with normal tissues. J Exp Clin Cancer Res. 31:542012. View Article : Google Scholar : PubMed/NCBI

14 

Liang Y: An expression meta-analysis of predicted microRNA targets identifies a diagnostic signature for lung cancer. BMC Med Genomics. 1:612008. View Article : Google Scholar : PubMed/NCBI

15 

Lin Y, Ge Y, Wang Y, Ma G, Wang X, Liu H, Wang M, Zhang Z and Chu H: The association of rs710886 in lncRNA PCAT1 with bladder cancer risk in a Chinese population. Gene. 627:226–232. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Altman DG, McShane LM, Sauerbrei W and Taube SE: Reporting recommendations for tumor marker prognostic studies (REMARK): Explanation and elaboration. PLoS Med. 9:e10012162012. View Article : Google Scholar : PubMed/NCBI

17 

Bouwmeester W, Zuithoff NP, Mallett S, Geerlings MI, Vergouwe Y, Steyerberg EW, Altman DG and Moons KG: Reporting and methods in clinical prediction research: A systematic review. PLoS Med. 9:1–12. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Chen G, Umelo IA, Lv S, Teugels E, Fostier K, Kronenberger P, Dewaele A, Sadones J, Geers C and De Grève J: miR-146α inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells. PLoS One. 8:e603172013. View Article : Google Scholar : PubMed/NCBI

19 

Chen Y, Min L, Ren C, Xu X, Yang J, Sun X, Wang T, Wang F, Sun C and Zhang X: miRNA-148α serves as a prognostic factor and suppresses migration and invasion through Wnt1 in non-small cell lung cancer. PLoS One. 12:e01717512017. View Article : Google Scholar : PubMed/NCBI

20 

Cui EH, Li HJ, Hua F, Wang B, Mao W, Feng XR, Li JY and Wang X: Serum microRNA 125b as a diagnostic or prognostic biomarker for advanced NSCLC patients receiving cisplatin-based chemotherapy. Acta Pharmacol Sin. 34:309–313. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Guo W, Zhang Y, Zhang Y, Shi Y, Xi J, Fan H and Xu S: Decreased expression of miR-204 in plasma is associated with a poor prognosis in patients with non-small cell lung cancer. Int J Mol Med. 36:1720–1726. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Li J, Yu T, Cao J, Liu L, Liu Y, Kong HW, Zhu MX, Lin HC, Chu DD, Yao M, et al: MicroRNA-148α suppresses invasion and metastasis of human non-small-cell lung cancer. Cell Physiol Biochem. 37:1847–1856. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Liu XG, Zhu WY, Huang YY, Ma LN, Zhou SQ, Wang YK, Zeng F, Zhou JH and Zhang YK: High expression of serum miR-21 and tumor miR-200c associated with poor prognosis in patients with lung cancer. Med Oncol. 29:618–626. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Nadal E, Zhong J, Lin J, Reddy RM, Ramnath N, Orringer MB, Chang AC, Beer DG and Chen G: A microRNA cluster at 14q32 drives aggressive lung adenocarcinoma. Clin Cancer Res. 20:3107–3117. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Skrzypski M, Czapiewski P, Goryca K, Jassem E, Wyrwicz L, Pawłowski R, Rzyman W, Biernat W and Jassem J: Prognostic value of microRNA expression in operable non-small cell lung cancer patients. Br J Cancer. 110:991–1000. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Sun Y, Su B, Zhang P, Xie H, Zheng H, Xu Y, Du Q, Zeng H, Zhou X, Chen C, et al: Expression of miR-150 and miR-3940-5p is reduced in non-small cell lung carcinoma and correlates with clinicopathological features. Oncol Rep. 29:704–712. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Võsa U, Vooder T, Kolde R, Fischer K, Välk K, Tõnisson N, Roosipuu R, Vilo J, Metspalu A and Annilo T: Identification of miR-374α as a prognostic marker for survival in patients with early-stage nonsmall cell lung cancer. Genes Chromosomes Cancer. 50:812–822. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Wang R, Ye F, Zhen Q, Song T, Tan G, Chu W, Zhang Y, Lv B, Zhao X and Liu J: MicroRNA-148b is a potential prognostic biomarker and predictor of response to radiotherapy in non-small-cell lung cancer. J Physiol Biochem. 72:337–343. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Jiang LP, Zhu ZT and He CY: Expression of miRNA-26b in the diagnosis and prognosis of patients with non-small-cell lung cancer. Future Oncol. 12:1105–1115. 2016. View Article : Google Scholar : PubMed/NCBI

30 

Rothschild SI, Tschan MP, Jaggi R, Fey MF, Gugger M and Gautschi O: microRNA-381 represses ID1 and is deregulated in lung adenocarcinoma. J Thorac Oncol. 7:1069–1077. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Al Khalaf MM, Thalib L and Doi SA: Combining heterogenous studies using the random-effects model is a mistake and leads to inconclusive meta-analyses. J Clin Epidemiol. 64:119–123. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Sittka A and Schmeck B: MicroRNAs in the lung. Adv Exp Med Biol. 774:121–134. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Wang T, Nelson RA, Bogardus A and Grannis FW Jr: Five-year lung cancer survival: Which advanced stage nonsmall cell lung cancer patients attain long-term survival? Cancer. 116:1518–1525. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Mizuno K, Mataki H, Seki N, Kumamoto T, Kamikawaji K and Inoue H: MicroRNAs in non-small cell lung cancer and idiopathic pulmonary fibrosis. J Hum Genet. 62:57–65. 2017. View Article : Google Scholar : PubMed/NCBI

35 

Gyoba J, Shan S, Roa W and Bédard EL: Diagnosing lung cancers through examination of micro-RNA biomarkers in blood, plasma, serum and sputum: A review and summary of current literature. Int J Mol Sci. 17:4942016. View Article : Google Scholar : PubMed/NCBI

36 

Wang X, Zhang Y, Fu Y, Zhang J, Yin L, Pu Y and Liang G: MicroRNA-125b may function as an oncogene in lung cancer cells. Mol Med Rep. 11:3880–3887. 2015. View Article : Google Scholar : PubMed/NCBI

37 

Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:2257–2261. 2006. View Article : Google Scholar : PubMed/NCBI

38 

Markou A, Zavridou M and Lianidou ES: miRNA-21 as a novel therapeutic target in lung cancer. Lung Cancer (Auckl). 7:19–27. 2016.PubMed/NCBI

39 

Mei Z, He Y, Feng J, Shi J, Du Y, Qian L, Huang Q and Jie Z: MicroRNA-141 promotes the proliferation of non-small cell lung cancer cells by regulating expression of PHLPP1 and PHLPP2. FEBS Lett. 588:3055–3061. 2014. View Article : Google Scholar : PubMed/NCBI

40 

Li J, Tan Q, Yan M, Liu L, Lin H, Zhao F, Bao G, Kong H, Ge C, Zhang F, et al: miRNA-200c inhibits invasion and metastasis of human non-small cell lung cancer by directly targeting ubiquitin specific peptidase 25. Mol Cancer. 13:1662014. View Article : Google Scholar : PubMed/NCBI

41 

Fiori ME, Barbini C, Haas TL, Marroncelli N, Patrizii M, Biffoni M and De Maria R: Antitumor effect of miR-197 targeting in p53 wild-type lung cancer. Cell Death Differ. 21:774–782. 2014. View Article : Google Scholar : PubMed/NCBI

42 

Du L, Schageman JJ, Subauste MC, Saber B, Hammond SM, Prudkin L, Wistuba II, Ji L, Roth JA, Minna JD, et al: miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1. Mol Cancer Res. 7:1234–1243. 2009. View Article : Google Scholar : PubMed/NCBI

43 

Remon J, Alvarez-Berdugo D, Majem M, Moran T, Reguart N and Lianes P: miRNA-197 and miRNA-184 are associated with brain metastasis in EGFR-mutant lung cancers. Clin Trans Oncol. 18:153–159. 2016. View Article : Google Scholar

44 

Chen T, Gao F, Feng S, Yang T and Chen M: MicroRNA-370 inhibits the progression of non-small cell lung cancer by downregulating oncogene TRAF4. Oncol Rep. 34:461–468. 2015. View Article : Google Scholar : PubMed/NCBI

45 

Wang Y, Cong W, Wu G, Ju X, Li Z, Duan X, Wang X and Gao H: miR-376α suppresses the proliferation and invasion of non-small-cell lung cancer by targeting c-Myc. Cell Biol Int. 42:25–33. 2018. View Article : Google Scholar : PubMed/NCBI

46 

Cao J, He Y, Liu HQ, Wang SB, Zhao BC and Cheng YS: MicroRNA 192 regulates chemo-resistance of lung adenocarcinoma for gemcitabine and cisplatin combined therapy by targeting Bcl-2. Int J Clin Exp Med. 8:12397–12403. 2015.PubMed/NCBI

47 

Tu C, Wang F and Wan J: MicroRNA-381 inhibits cell proliferation and invasion in endometrial carcinoma by targeting the IGF-1R. Mol Med Rep. 17:4090–4098. 2018.PubMed/NCBI

48 

Shi L, Xu Z, Wu G, Chen X, Huang Y, Wang Y, Jiang W and Ke B: Up-regulation of miR-146α increases the sensitivity of non-small cell lung cancer to DDP by downregulating cyclin J. BMC Cancer. 17:1382017. View Article : Google Scholar : PubMed/NCBI

49 

Zhai G, Li G, Xu B, Jia T, Sun Y, Zheng J and Li J: miRNA-148b regulates radioresistance in non-small lung cancer cells via regulation of MutL homologue 1. Biosci Rep. 36:e003542016. View Article : Google Scholar : PubMed/NCBI

50 

Zhang S, Gao L, Thakur A, Shi P, Liu F, Feng J, Wang T, Liang Y, Liu JJ, Chen M, et al: miRNA-204 suppresses human non-small cell lung cancer by targeting ATF2. Tumour Biol. 37:11177–11186. 2016. View Article : Google Scholar : PubMed/NCBI

51 

Cheng J, Chen Y, Zhao P, Liu X, Dong J, Li J, Huang C, Wu R and Lv Y: Downregulation of miRNA-638 promotes angiogenesis and growth of hepatocellular carcinoma by targeting VEGF. Oncotarget. 7:30702–30711. 2016.PubMed/NCBI

52 

Shi GL, Chen Y, Sun Y, Yin YJ and Song CX: Significance of serum microRNAs in the auxiliary diagnosis of non-small cell lung cancer. Clin Lab. 63:133–140. 2017. View Article : Google Scholar : PubMed/NCBI

53 

Zhan B, Lu D, Luo P and Wang B: Prognostic value of expression of microRNAs in non-small cell lung cancer: A systematic review and meta-analysis. Clin Lab. 62:2203–2211. 2016. View Article : Google Scholar : PubMed/NCBI

54 

Yu N, Zhang Q, Liu Q, Yang J and Zhang S: A meta-analysis: microRNAs' prognostic function in patients with nonsmall cell lung cancer. Cancer Med. 6:2098–2105. 2017. View Article : Google Scholar : PubMed/NCBI

55 

Jiang M, Li X, Quan X, Li Xi and Zhou B: Clinically correlated microRNAs in the diagnosis of non-small cell lung cancer: A systematic review and meta-analysis. Biomed Res Int. 2018:59309512018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
APA
Xiao, W., Zhong, Y., Wu, L., Yang, D., Ye, S., & Zhang, M. (2019). Prognostic value of microRNAs in lung cancer: A systematic review and meta‑analysis. Molecular and Clinical Oncology, 10, 67-77. https://doi.org/10.3892/mco.2018.1763
MLA
Xiao, W., Zhong, Y., Wu, L., Yang, D., Ye, S., Zhang, M."Prognostic value of microRNAs in lung cancer: A systematic review and meta‑analysis". Molecular and Clinical Oncology 10.1 (2019): 67-77.
Chicago
Xiao, W., Zhong, Y., Wu, L., Yang, D., Ye, S., Zhang, M."Prognostic value of microRNAs in lung cancer: A systematic review and meta‑analysis". Molecular and Clinical Oncology 10, no. 1 (2019): 67-77. https://doi.org/10.3892/mco.2018.1763