title: Up-regulation of miR-9 expression as a poor prognostic biomarker in patients with non-small cell lung cancer.
abstract: OBJECTIVE
  Emerging evidences indicate that dysregulated microRNAs are implicated in cancer tumorigenesis and progression. MicroRNA-9 (miR-9) has various expression patterns in diverse human cancers. However, its clinical significance in human non-small cell lung cancer has not yet been elucidated. In the present study, we detected the expression of miR-9 in non-small cell lung cancer and adjacent noncancerous tissues and explored its relationships with clinicopathological characteristics and prognosis.
  
  
  METHODS
  Expression levels of miR-9 in 116 pairs of non-small cell lung cancer and adjacent normal tissues were detected by real-time quantitative RT-PCR assay. To determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis.
  
  
  RESULTS
  MiR-9 expression in non-small cell lung cancer tissues was significantly higher than that in adjacent normal tissues (p = 0.001), and its up-regulation was significantly correlated to advanced tumor-node-metastasis (TNM) stage (p < 0.001), tumor size (p = 0.013), and lymph node metastasis (p = 0.001). Furthermore, Kaplan-Meier analysis demonstrated that high miR-9 expression clearly predicted poorer PFS (p < 0.001) and OS (p < 0.001). In the multivariate analysis, increased miR-9 expression was an independent prognostic factor for both PFS (p = 0.002) and OS (p = 0.013).
  
  
  CONCLUSIONS
  MiR-9 was up-regulated in non-small cell lung cancer tissues and correlated with adverse clinical features and unfavorable survival, indicating that miR-9 might be involved in non-small lung cancer progression and could serve as a promising biomarker for further risk stratification in the treatment of this cancer.
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, People's Republic of China.
authors.forename: T
authors.initials: T
authors.lastname: Xu
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Han
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Shu
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015996:Survival Rate; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C541874:MIRN92 microRNA, human; D035683:MicroRNAs
references.citation: N Engl J Med. 2005 Jun 23;352(25):2589-97
references.pmid: 15972865
references.citation: Int J Cancer. 2011 Jan 1;128(1):132-43
references.pmid: 20309880
references.citation: Brain Pathol. 2009 Jul;19(3):375-83
references.pmid: 18624795
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):264-9
references.pmid: 20018759
references.citation: Cancer Res. 2010 Apr 1;70(7):2728-38
references.pmid: 20332243
references.citation: Cancer Res. 2013 Jan 15;73(2):756-66
references.pmid: 23204228
references.citation: Cancer Res Treat. 2004 Feb;36(1):56-61
references.pmid: 20396566
references.citation: Nat Rev Genet. 2004 Jul;5(7):522-31
references.pmid: 15211354
references.citation: N Engl J Med. 2004 Jan 22;350(4):351-60
references.pmid: 14736927
references.citation: Neoplasia. 2012 Sep;14(9):868-79
references.pmid: 23019418
references.citation: J Thorac Oncol. 2007 Aug;2(8):706-14
references.pmid: 17762336
references.citation: Lung Cancer. 2013 May;80(2):223-7
references.pmid: 23410826
references.citation: Genes Chromosomes Cancer. 2011 Oct;50(10):812-22
references.pmid: 21748820
references.citation: PLoS One. 2011;6(8):e23584
references.pmid: 21858175
references.citation: Cancer Cell. 2006 Mar;9(3):189-98
references.pmid: 16530703
references.citation: Methods. 2013 Jan;59(1):138-46
references.pmid: 22989523
references.citation: Oncogene. 2010 Oct 21;29(42):5724-8
references.pmid: 20676129
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2257-61
references.pmid: 16461460
references.citation: Nat Rev Cancer. 2006 Apr;6(4):259-69
references.pmid: 16557279
references.citation: PLoS One. 2012;7(6):e39011
references.pmid: 22723919
references.citation: PLoS One. 2013;8(1):e55719
references.pmid: 23383271
references.citation: PLoS One. 2012;7(10):e46890
references.pmid: 23071657
references.citation: Cancer Res. 2010 Feb 15;70(4):1441-8
references.pmid: 20124485
references.citation: Nat Cell Biol. 2010 Mar;12(3):247-56
references.pmid: 20173740
references.citation: Biochim Biophys Acta. 2013 Jun;1830(6):3756-66
references.pmid: 23458685
references.citation: N Engl J Med. 2004 Apr 22;350(17):1713-21
references.pmid: 15102997
references.citation: Nat Rev Cancer. 2006 Nov;6(11):857-66
references.pmid: 17060945
references.citation: N Engl J Med. 2000 Nov 30;343(22):1627-33
references.pmid: 11096172
references.citation: CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66
references.pmid: 17237035
references.citation: FEBS J. 2009 Oct;276(19):5537-46
references.pmid: 19702828