title: Identification of a 5-gene signature for clinical and prognostic prediction in gastric cancer patients upon microarray data.
abstract: In this study, we aimed to investigate the clinical and prognostic value of a 5-gene expression signature model for gastric cancer patients upon microarray data. A total of 158 gastric cancer patients were selected, with 33 cases used for microarray analysis as training set and 125 cases for validation real-time quantitative polymerase chain reaction analysis as test set. Unsupervised clustering algorithms and supervised clustering algorithm were used to identify differentially expressed genes. Gene ontology analyses were used to determine functional prediction of gene biomarkers and receiver operating characteristic analyses to verify the specificity and sensitivity of the evaluation. Moreover, the correlation between clinicopathological characteristics and 5-gene expression was evaluated. The results showed that there were poor disease progression and clinic prognosis in the patients with proximal gastric cancer compared with distal gastric cancer, including differentiation grade (P = 0.001), depth of tumor invasion (P < 0.01), lymph node metastasis (P < 0.01), UICC stage (P < 0.01), and survival status (P < 0.01). Furthermore, a 5-gene signature, including cordon-bleu protein-like 1, damage-specific DNA binding protein 1, BCL2-like 13, nuclear receptor coactivator-6, and F-box leucine-rich protein 11, was identified based on the combination of multiple bioinformatics algorithm. The expression of 5-gene signature (HR = 2.35; 95 % confidence interval 1.24-5.06; P = 0.026) and UICC stage (HR = 5.35; 95 % confidence interval 1.36-19.15; P = 0.032) was independent prognostic factors for overall survival in the survival multivariate analysis. Over-expression of the 5-gene signature in patients with proximal gastric cancer is strongly associated with disease progression and poor prognosis, suggesting that might be potential prognostic predictors in gastric cancer.
authors.affiliation: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, 627 Wuluo Road, Wuhan 430070, People's Republic of China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yan
authors.forename: Bicheng
authors.initials: B
authors.lastname: Zhang
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Rao
authors.forename: Yafei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Lifang
authors.initials: L
authors.lastname: Yu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.forename: Jianfei
authors.initials: J
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D044783:F-Box Proteins / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D056918:Nuclear Receptor Coactivators / Q000235:genetics; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: C431152:BCL2L13 protein, human; D014408:Biomarkers, Tumor; C584084:COBLL1 protein, human; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; C486559:NCOA6 protein, human; D056918:Nuclear Receptor Coactivators; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors
references.citation: Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):612-20
references.pmid: 15701848
references.citation: Nat Cell Biol. 2004 Oct;6(10):1003-9
references.pmid: 15448697
references.citation: Blood. 2006 Jan 15;107(2):769-76
references.pmid: 16189266
references.citation: Recent Results Cancer Res. 2010;182:1-17
references.pmid: 20676867
references.citation: Ann Surg Oncol. 2008 Jun;15(6):1644-50
references.pmid: 18392661
references.citation: Br J Cancer. 2008 Oct 21;99(8):1307-15
references.pmid: 18827816
references.citation: Cancer Lett. 2008 Aug 8;266(2):99-115
references.pmid: 18381231
references.citation: J Am Coll Surg. 2008 Feb;206(2):306-10
references.pmid: 18222384
references.citation: Clin Cancer Res. 2010 Jan 15;16(2):451-60
references.pmid: 20068093
references.citation: Hum Pathol. 2011 Dec;42(12):1937-45
references.pmid: 21676433
references.citation: Med Oncol. 2012 Mar;29(1):77-83
references.pmid: 21132402
references.citation: Int J Biol Sci. 2011 Apr 19;7(5):505-16
references.pmid: 21552418
references.citation: Anticancer Res. 2013 Apr;33(4):1257-66
references.pmid: 23564763
references.citation: J Gastrointest Surg. 2012 Mar;16(3):503-8
references.pmid: 22215245
references.citation: Br J Cancer. 2007 Feb 26;96(4):631-8
references.pmid: 17262083
references.citation: Mol Oncol. 2007 Jun;1(1):26-41
references.pmid: 19383285
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16339-44
references.pmid: 19805303
references.citation: J Natl Cancer Inst. 2009 May 6;101(9):678-86
references.pmid: 19401544
references.citation: Cancer Biomark. 2013;13(1):11-20
references.pmid: 23736017
references.citation: Biometrics. 2003 Mar;59(1):133-42
references.pmid: 12762450
references.citation: Clin Cancer Res. 2011 May 1;17(9):2693-701
references.pmid: 21430069
references.citation: Cancer Biomark. 2011-2012;10(2):71-7
references.pmid: 22430134
references.citation: CA Cancer J Clin. 2005 Nov-Dec;55(6):334-51
references.pmid: 16282279
references.citation: Cancer. 2013 Jun 1;119(11):1985-93
references.pmid: 23456798
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
references.pmid: 9843981
references.citation: Med Oncol. 2010 Dec;27(4):1192-9
references.pmid: 19924575
references.citation: PLoS One. 2013 May 22;8(5):e63826
references.pmid: 23717493
references.citation: Am J Gastroenterol. 2011 Nov;106(11):1978-85
references.pmid: 22008896
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Clin Cancer Res. 2011 Apr 1;17(7):1850-7
references.pmid: 21447720
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
references.pmid: 11309499
references.citation: Brief Bioinform. 2005 Dec;6(4):318-30
references.pmid: 16420731
references.citation: Ann Surg Oncol. 2006 Jan;13(1):12-30
references.pmid: 16378161
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22237-42
references.pmid: 21135245
references.citation: FEBS Lett. 2003 Jan 16;534(1-3):61-8
references.pmid: 12527362
references.citation: J Clin Oncol. 2012 Oct 1;30(28):3507-15
references.pmid: 22949151
references.citation: Nucl Recept Signal. 2008 Feb 01;6:e002
references.pmid: 18301782
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):46-51
references.pmid: 20080798