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Published in: Journal of Ovarian Research 1/2017

Open Access 01-12-2017 | Research

Bioinformatics analysis to screen the key prognostic genes in ovarian cancer

Authors: Li Li, Shengyun Cai, Shengnan Liu, Hao Feng, Junjie Zhang

Published in: Journal of Ovarian Research | Issue 1/2017

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Abstract

Background

Ovarian cancer (OC) is a gynecological oncology that has a poor prognosis and high mortality. This study is conducted to identify the key genes implicated in the prognosis of OC by bioinformatic analysis.

Methods

Gene expression data (including 568 primary OC tissues, 17 recurrent OC tissues, and 8 adjacent normal tissues) and the relevant clinical information of OC patients were downloaded from The Cancer Genome Atlas database. After data preprocessing, cluster analysis was conducted using the ConsensusClusterPlus package in R. Using the limma package in R, differential analysis was performed to identify feature genes. Based on Kaplan-Meier (KM) survival analysis, prognostic seed genes were selected from the feature genes. After key prognostic genes were further screened by cluster analysis and KM survival analysis, they were performed functional enrichment analysis and multivariate survival analysis. Using the survival package in R, cox regression analysis was conducted for the microarray data of GSE17260 to validate the key prognostic genes.

Results

A total of 3668 feature genes were obtained, among which 75 genes were identified as prognostic seed genes. Then, 25 key prognostic genes were screened, including AXL, FOS, KLF6, WDR77, DUSP1, GADD45B, and SLIT3. Especially, AXL and SLIT3 were enriched in ovulation cycle. Multivariate survival analysis showed that the key prognostic genes could effectively differentiate the samples and were significantly associated with prognosis. Additionally, GSE17260 confirmed that the key prognostic genes were associated with the prognosis of OC.

Conclusion

AXL, FOS, KLF6, WDR77, DUSP1, GADD45B, and SLIT3 might affect the prognosis of OC.
Literature
1.
go back to reference Modugno F, Edwards RP. Ovarian cancer: prevention, detection, and treatment of the disease and its recurrence. Molecular mechanisms and personalized medicine meeting report. Int J Gynecol Cancer. 2012;22(8):45–57.CrossRef Modugno F, Edwards RP. Ovarian cancer: prevention, detection, and treatment of the disease and its recurrence. Molecular mechanisms and personalized medicine meeting report. Int J Gynecol Cancer. 2012;22(8):45–57.CrossRef
2.
go back to reference Cancer UK. Treating advanced ovarian cancer. 2014. Cancer UK. Treating advanced ovarian cancer. 2014.
3.
go back to reference Mcguire S. World Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Advances in Nutrition. 2016;7(2):418–9.CrossRefPubMedPubMedCentral Mcguire S. World Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015. Advances in Nutrition. 2016;7(2):418–9.CrossRefPubMedPubMedCentral
4.
5.
go back to reference Li J, Jiang K, Qiu X, et al. Overexpression of CXCR4 is significantly associated with cisplatin-based chemotherapy resistance and can be a prognostic factor in epithelial ovarian cancer. BMB Rep. 2014;47(1):33–8.CrossRefPubMedPubMedCentral Li J, Jiang K, Qiu X, et al. Overexpression of CXCR4 is significantly associated with cisplatin-based chemotherapy resistance and can be a prognostic factor in epithelial ovarian cancer. BMB Rep. 2014;47(1):33–8.CrossRefPubMedPubMedCentral
6.
go back to reference Xia Y, Chang T, Wang Y, et al. YAP Promotes Ovarian Cancer Cell Tumorigenesis and Is Indicative of a Poor Prognosis for Ovarian Cancer Patients. Plos One. 2014;9(3):e91770.CrossRefPubMedPubMedCentral Xia Y, Chang T, Wang Y, et al. YAP Promotes Ovarian Cancer Cell Tumorigenesis and Is Indicative of a Poor Prognosis for Ovarian Cancer Patients. Plos One. 2014;9(3):e91770.CrossRefPubMedPubMedCentral
7.
go back to reference Tan G, Cao X, Dai Q, et al. A novel role for microRNA-129-5p in inhibiting ovarian cancer cell proliferation and survival via direct suppression of transcriptional co-activators YAP and TAZ. Oncotarget. 2015;6(11):8676–86.CrossRefPubMedPubMedCentral Tan G, Cao X, Dai Q, et al. A novel role for microRNA-129-5p in inhibiting ovarian cancer cell proliferation and survival via direct suppression of transcriptional co-activators YAP and TAZ. Oncotarget. 2015;6(11):8676–86.CrossRefPubMedPubMedCentral
8.
9.
go back to reference Zhao Y, Chen S, Gou WF, Xiao LJ, Takano Y, Zheng HC. Aberrant Beclin 1 expression is closely linked to carcinogenesis, differentiation, progression, and prognosis of ovarian epithelial carcinoma. Tumor Biology. 2014;35(3):1955–64.CrossRefPubMed Zhao Y, Chen S, Gou WF, Xiao LJ, Takano Y, Zheng HC. Aberrant Beclin 1 expression is closely linked to carcinogenesis, differentiation, progression, and prognosis of ovarian epithelial carcinoma. Tumor Biology. 2014;35(3):1955–64.CrossRefPubMed
10.
go back to reference Califano D, Pignata S, Losito NS, et al. High HMGA2 Expression and High Body Mass Index Negatively Affect the Prognosis of Patients With Ovarian Cancer. J Cell Physiol. 2014;229(1):53–9.PubMed Califano D, Pignata S, Losito NS, et al. High HMGA2 Expression and High Body Mass Index Negatively Affect the Prognosis of Patients With Ovarian Cancer. J Cell Physiol. 2014;229(1):53–9.PubMed
11.
go back to reference Ning W, Yu W, Li W, et al. Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell proliferation, migration and invasion in epithelial ovarian cancer. J Transl Med. 2014;12(1):1–13.CrossRef Ning W, Yu W, Li W, et al. Overexpression of FOXM1 predicts poor prognosis and promotes cancer cell proliferation, migration and invasion in epithelial ovarian cancer. J Transl Med. 2014;12(1):1–13.CrossRef
12.
go back to reference Zhao F, Siu MK, Jiang L, et al. Overexpression of forkhead box protein M1 (FOXM1) in ovarian cancer correlates with poor patient survival and contributes to paclitaxel resistance. Plos One. 2014;9(11):e113478.CrossRefPubMedPubMedCentral Zhao F, Siu MK, Jiang L, et al. Overexpression of forkhead box protein M1 (FOXM1) in ovarian cancer correlates with poor patient survival and contributes to paclitaxel resistance. Plos One. 2014;9(11):e113478.CrossRefPubMedPubMedCentral
13.
go back to reference Network CGAR. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489(7417):519–25.CrossRef Network CGAR. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489(7417):519–25.CrossRef
14.
go back to reference Wilkerson MD, Hayes DN. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics. 2010;26(12):1572–3.CrossRefPubMedPubMedCentral Wilkerson MD, Hayes DN. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics. 2010;26(12):1572–3.CrossRefPubMedPubMedCentral
15.
go back to reference Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.
16.
go back to reference Lacny S, Wilson T, Clement F, et al. Kaplan-Meier Survival Analysis Overestimates the Risk of Revision Arthroplasty: A Meta-analysis. Clin Orthop Relat Res. 2015;473(11):3431–42.CrossRefPubMedPubMedCentral Lacny S, Wilson T, Clement F, et al. Kaplan-Meier Survival Analysis Overestimates the Risk of Revision Arthroplasty: A Meta-analysis. Clin Orthop Relat Res. 2015;473(11):3431–42.CrossRefPubMedPubMedCentral
17.
go back to reference Carbon S, Ireland A, Mungall CJ, et al. AmiGO: online access to ontology and annotation data. Bioinformatics. 2009;25(2):288–9.CrossRefPubMed Carbon S, Ireland A, Mungall CJ, et al. AmiGO: online access to ontology and annotation data. Bioinformatics. 2009;25(2):288–9.CrossRefPubMed
18.
go back to reference Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics A Journal of Integrative Biology. 2012;16(5):284–7.CrossRefPubMedPubMedCentral Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics A Journal of Integrative Biology. 2012;16(5):284–7.CrossRefPubMedPubMedCentral
19.
go back to reference Heagerty PJ, Thomas L, Pepe MS. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 2000;56(2):337–44.CrossRefPubMed Heagerty PJ, Thomas L, Pepe MS. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 2000;56(2):337–44.CrossRefPubMed
20.
go back to reference Akira M, Yuya M, Yoshihisa N, et al. Kaplan–Meier survival analysis and Cox regression analyses regarding right ventricular septal pacing: Data from Japanese pacemaker cohort. Data Brief. 2016;8:1303–7.CrossRef Akira M, Yuya M, Yoshihisa N, et al. Kaplan–Meier survival analysis and Cox regression analyses regarding right ventricular septal pacing: Data from Japanese pacemaker cohort. Data Brief. 2016;8:1303–7.CrossRef
21.
go back to reference Tamura RE, de Vasconcellos JF, Sarkar D, Libermann TA, Fisher PB, Zerbini LF. GADD45 proteins: central players in tumorigenesis. Curr Mol Med. 2012;12(5):634–51.CrossRefPubMedPubMedCentral Tamura RE, de Vasconcellos JF, Sarkar D, Libermann TA, Fisher PB, Zerbini LF. GADD45 proteins: central players in tumorigenesis. Curr Mol Med. 2012;12(5):634–51.CrossRefPubMedPubMedCentral
22.
go back to reference Salvador JM, Brown-Clay JD, Fornace AJ. Gadd45 in Stress Signaling, Cell Cycle Control, and Apoptosis. Adv Exp Med Biol. 2013;793(10):1–19.CrossRefPubMed Salvador JM, Brown-Clay JD, Fornace AJ. Gadd45 in Stress Signaling, Cell Cycle Control, and Apoptosis. Adv Exp Med Biol. 2013;793(10):1–19.CrossRefPubMed
23.
go back to reference Jiang T, Soprano DR, Soprano KJ. GADD45A is a mediator of CD437 induced apoptosis in ovarian carcinoma cells. J Cell Physiol. 2007;212(3):771–9.CrossRefPubMed Jiang T, Soprano DR, Soprano KJ. GADD45A is a mediator of CD437 induced apoptosis in ovarian carcinoma cells. J Cell Physiol. 2007;212(3):771–9.CrossRefPubMed
24.
25.
go back to reference Mahner S, Baasch C, Schwarz J, et al. C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma. Br J Cancer. 2008;99(8):1269–75.CrossRefPubMedPubMedCentral Mahner S, Baasch C, Schwarz J, et al. C-Fos expression is a molecular predictor of progression and survival in epithelial ovarian carcinoma. Br J Cancer. 2008;99(8):1269–75.CrossRefPubMedPubMedCentral
26.
go back to reference Difeo A, Narla G, Hirshfeld J, et al. Roles of KLF6 and KLF6-SV1 in ovarian cancer progression and intraperitoneal dissemination. Clin Cancer Res. 2006;12(12):3730–9.CrossRefPubMed Difeo A, Narla G, Hirshfeld J, et al. Roles of KLF6 and KLF6-SV1 in ovarian cancer progression and intraperitoneal dissemination. Clin Cancer Res. 2006;12(12):3730–9.CrossRefPubMed
27.
go back to reference Ligr M, Patwa RR, Daniels G, et al. Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer. Plos One. 2011;6(10):e26250.CrossRefPubMedPubMedCentral Ligr M, Patwa RR, Daniels G, et al. Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer. Plos One. 2011;6(10):e26250.CrossRefPubMedPubMedCentral
28.
go back to reference Kang YS, Seok HJ, Jeong EJ, et al. DUSP1 induces paclitaxel resistance through the regulation of p-glycoprotein expression in human ovarian cancer cells. Biochem Biophys Res Commun. 2016;478(1):403–9.CrossRefPubMed Kang YS, Seok HJ, Jeong EJ, et al. DUSP1 induces paclitaxel resistance through the regulation of p-glycoprotein expression in human ovarian cancer cells. Biochem Biophys Res Commun. 2016;478(1):403–9.CrossRefPubMed
29.
go back to reference Kang Y, Nagaraja AS, Armaizpena GN, et al. Adrenergic stimulation of DUSP1 impairs chemotherapy response in ovarian cancer. Clin Cancer Res. 2015;22(7):1713–24. Kang Y, Nagaraja AS, Armaizpena GN, et al. Adrenergic stimulation of DUSP1 impairs chemotherapy response in ovarian cancer. Clin Cancer Res. 2015;22(7):1713–24.
30.
go back to reference Melhem A, Yamada SD, Fleming GF, et al. Administration of glucocorticoids to ovarian cancer patients is associated with expression of the anti-apoptotic genes SGK1 and MKP1/DUSP1 in ovarian tissues. Clin Cancer Res. 2009;15(9):3196–204.CrossRefPubMedPubMedCentral Melhem A, Yamada SD, Fleming GF, et al. Administration of glucocorticoids to ovarian cancer patients is associated with expression of the anti-apoptotic genes SGK1 and MKP1/DUSP1 in ovarian tissues. Clin Cancer Res. 2009;15(9):3196–204.CrossRefPubMedPubMedCentral
31.
go back to reference Wang J, Zhou JY, Wu GS. ERK-dependent MKP-1-mediated cisplatin resistance in human ovarian cancer cells. Cancer Res. 2007;67(24):11933–41.CrossRefPubMed Wang J, Zhou JY, Wu GS. ERK-dependent MKP-1-mediated cisplatin resistance in human ovarian cancer cells. Cancer Res. 2007;67(24):11933–41.CrossRefPubMed
32.
go back to reference Sun W, Fujimoto J, Tamaya T. Coexpression of Gas6/Axl in Human Ovarian Cancers. Oncology. 2004;66(6):450–7.CrossRefPubMed Sun W, Fujimoto J, Tamaya T. Coexpression of Gas6/Axl in Human Ovarian Cancers. Oncology. 2004;66(6):450–7.CrossRefPubMed
33.
go back to reference Rankin EB, Fuh KCTaylor TE, Krieg AJ, et al. AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Res. 2010;70(19):7570–9.CrossRefPubMedPubMedCentral Rankin EB, Fuh KCTaylor TE, Krieg AJ, et al. AXL is an essential factor and therapeutic target for metastatic ovarian cancer. Cancer Res. 2010;70(19):7570–9.CrossRefPubMedPubMedCentral
34.
go back to reference Dickinson RE, Fegan KS, Ren X, Hillier SG, Duncan WC. Glucocorticoid Regulation of SLIT/ROBO Tumour Suppressor Genes in the Ovarian Surface Epithelium and Ovarian Cancer Cells. Plos One. 2011;6(11):e27792.CrossRefPubMedPubMedCentral Dickinson RE, Fegan KS, Ren X, Hillier SG, Duncan WC. Glucocorticoid Regulation of SLIT/ROBO Tumour Suppressor Genes in the Ovarian Surface Epithelium and Ovarian Cancer Cells. Plos One. 2011;6(11):e27792.CrossRefPubMedPubMedCentral
35.
go back to reference Dickinson RE, Myers M, Duncan WC. Novel regulated expression of the SLIT/ROBO pathway in the ovary: possible role during luteolysis in women. Endocrinology. 2008;149(10):5024–34.CrossRefPubMed Dickinson RE, Myers M, Duncan WC. Novel regulated expression of the SLIT/ROBO pathway in the ovary: possible role during luteolysis in women. Endocrinology. 2008;149(10):5024–34.CrossRefPubMed
36.
go back to reference Qiu H, Zhu J, Yu J, Pu H, Dong R. SLIT2 is epigenetically silenced in ovarian cancers and suppresses growth when activated. Asian Pac J Cancer Prev. 2011;12(3):791–5.PubMed Qiu H, Zhu J, Yu J, Pu H, Dong R. SLIT2 is epigenetically silenced in ovarian cancers and suppresses growth when activated. Asian Pac J Cancer Prev. 2011;12(3):791–5.PubMed
Metadata
Title
Bioinformatics analysis to screen the key prognostic genes in ovarian cancer
Authors
Li Li
Shengyun Cai
Shengnan Liu
Hao Feng
Junjie Zhang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2017
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-017-0323-6

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