title: Increased BCAR1 predicts poor outcomes of non-small cell lung cancer in multiple-center patients.
abstract: OBJECTIVE
  This study was designed to determine the prognostic value of BCAR1 expression and its associations with clinical-demographical characteristics in multiple centers of non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  Gene expression microarray (mRNA) of 77 adenocarcinomas from Mayo Clinic, RNA-sequencing of 508 NSCLC from The Cancer Genome Atlas (TCGA), and immunohistochemistry stain of BCAR1-protein expression in 150 cases from Daping Hospital were included in the study. The association of mRNA or protein expression with patient clinical characteristics and overall survival was assessed in each dataset. We also predicted microRNAs (miRNA) that target BCAR1 using bioinformatics prediction tools and evaluated miRNA expression patterns with BCAR1 expression in miRNA-sequencing data of 74 lung cancer cases from TCGA dataset.
  
  
  RESULTS
  In the Mayo Clinic dataset, a higher BCAR1-mRNA level correlated significantly with more advanced tumor-stage and lymphatic metastasis. Similar changes were observed in the TCGA RNA-seq dataset. Additionally, higher BCAR1-mRNA levels predicted poorer survival in adenocarcinoma and squamous carcinoma from the TCGA dataset. The protein levels in the adenocarcinoma cases with lymphatic metastasis were significantly higher than of those without metastasis. Tumor tissues demonstrated remarkably higher levels of protein compared with matched normal tissues although there was no significant difference in BCAR1-mRNA expression between tumor and matched normal tissues was detected. In miRNAs that were downregulated in the tumors, Let-7f-2 and miR-22 differed the most (P < 0.001 and P = 0.007, respectively).
  
  
  CONCLUSIONS
  We confirmed that increased BCAR1 expression predicts poorer prognosis in NSCLC. We postulate that mRNA-protein decoupling of BCAR1 may be a result of reduced inhibition of specific miRNAs in tumor tissues, which warrants further study.
authors.affiliation: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, College of Medicine, Rochester, MN, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Deng
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Sun
authors.forename: Wampfler
authors.initials: W
authors.lastname: Jason
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D050719:Crk-Associated Substrate Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: C493841:BCAR1 protein, human; D014408:Biomarkers, Tumor; D050719:Crk-Associated Substrate Protein; D035683:MicroRNAs
references.citation: Clin Exp Metastasis. 2012 Aug;29(6):527-40
references.pmid: 22476538
references.citation: J Biomed Inform. 2011 Oct;44(5):839-47
references.pmid: 21605702
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D149-53
references.pmid: 18158296
references.citation: Clin Cancer Res. 2004 Sep 15;10(18 Pt 1):6194-202
references.pmid: 15448007
references.citation: Mol Diagn Ther. 2011 Feb 1;15(1):31-40
references.pmid: 21469768
references.citation: Folia Histochem Cytobiol. 2012 Oct 08;50(3):392-7
references.pmid: 23042269
references.citation: BMC Genomics. 2012 Nov 21;13:656
references.pmid: 23170974
references.citation: Inflammation. 2012 Aug;35(4):1308-13
references.pmid: 22415194
references.citation: J Natl Cancer Inst. 2000 Jan 19;92(2):112-20
references.pmid: 10639512
references.citation: Bioinformatics. 2012 Dec 15;28(24):3322-3
references.pmid: 23074262
references.citation: J Cell Biochem. 2002;87(4):439-49
references.pmid: 12397603
references.citation: Cancer Res. 2006 May 1;66(9):4672-80
references.pmid: 16651418
references.citation: Mol Cell Biol. 1989 Feb;9(2):629-38
references.pmid: 2469003
references.citation: Breast Cancer (Dove Med Press). 2009 Dec 07;1:39-52
references.pmid: 24367162
references.citation: Mol Cell Biol. 1991 Feb;11(2):713-20
references.pmid: 1703631
references.citation: J Renin Angiotensin Aldosterone Syst. 2013 Jun;14(2):97-102
references.pmid: 23087255
references.citation: Biochim Biophys Acta. 2004 Jul 5;1692(2-3):63-76
references.pmid: 15246680
references.citation: FASEB J. 2010 Oct;24(10):3796-808
references.pmid: 20505116
references.citation: Prostate. 2007 Feb 15;67(3):268-73
references.pmid: 17192874
references.citation: Neoplasia. 2012 Feb;14(2):108-20
references.pmid: 22431919
references.citation: J Natl Cancer Inst. 2011 Nov 2;103(21):1596-612
references.pmid: 21957230
references.citation: Int J Bioinform Res Appl. 2012;8(3-4):171-91
references.pmid: 22961450
references.citation: Mol Biol Cell. 2008 May;19(5):2135-46
references.pmid: 18321991
references.citation: Dis Esophagus. 2013 Jul;26(5):528-37
references.pmid: 22816673
references.citation: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W145-8
references.pmid: 21551220
references.citation: Hepatobiliary Pancreat Dis Int. 2008 Oct;7(5):490-6
references.pmid: 18842495
references.citation: Breast Cancer Res Treat. 2010 Apr;120(2):401-8
references.pmid: 19412734
references.citation: Lancet Oncol. 2010 Apr;11(4):321-30
references.pmid: 20304703
references.citation: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W451-4
references.pmid: 16845047
references.citation: PLoS One. 2012;7(4):e36124
references.pmid: 22558353
references.citation: Mol Cell Biochem. 2011 Nov;357(1-2):151-61
references.pmid: 21630091