nach oben

Archives of Gynecology and Obstetrics

Erschienen in:

01.10.2014 | Gynecologic Oncology

Construction of breast cancer gene regulatory networks and drug target optimization

verfasst von: Yishan Xie, Rui Wang, Jian Zhu

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 4/2014

Einloggen, um Zugang zu erhalten

Abstract

Objective

The purpose of this study was to construct the breast cancer gene regulatory networks through the high-throughput techniques and optimize the drug target genes of breast cancer using bioinformatics analysis, and thus accelerate the process of drug development and improve the cure rate of breast cancer.

Methods

The gene expression profile data of breast cancer were downloaded from GEO database and the transcriptional regulation data were obtained from UCSC database. Then we identified the differentially expressed genes (DEGs) by SAM algorithm and built gene regulatory networks by the supervised algorithm SIRENE. Finally, the drug targets of the DEGs with changed regulation relations were optimized based on the CancerResource database.

Results

A total of 584 DEGs were identified and the gene regulatory networks in the normal state and tumorous state were constructed. By comparing the new predicted regulatory relation in cancer state and normal state, the regulatory relation of 18 genes was found to be changed in the two states, showing the possibility to be applied as drug target genes. After the searches in the CancerResources, 7 genes were screened as the drug target genes, such as PFKFB3.

Conclusion

Our present findings shed new light on the molecular mechanism of breast cancer and provide some drug targets which have the potential to be used in clinic for the treatment of breast cancer in future.

Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30PubMedCrossRef

Levin AO (2013) The impact of reduced ovarian function and its consequences on young women survivors of breast and gynecologic cancer. In: The Ohio State University

Bleyer A, Welch HG (2012) Effect of three decades of screening mammography on breast-cancer incidence. N Engl J Med 367(21):1998–2005PubMedCrossRef

Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S (2012) Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 62(4):220–241PubMedCrossRef

Stephens PJ, Tarpey PS, Davies H, Van Loo P, Greenman C, Wedge DC, Nik-Zainal S, Martin S, Varela I, Bignell GR (2012) The landscape of cancer genes and mutational processes in breast cancer. Nature 486(7403):400–404PubMedCentralPubMed

Reis-Filho JS, Pusztai L (2011) Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet 378(9805):1812–1823PubMedCrossRef

Weigelt B, Baehner FL, Reis-Filho JS (2010) The contribution of gene expression profiling to breast cancer classification, prognostication and prediction: a retrospective of the last decade. J Pathol 220(2):263–280PubMed

Goldhirsch A, Wood W, Coates A, Gelber R, Thürlimann B, Senn H-J (2011) Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol 22(8):1736–1747PubMedCentralPubMedCrossRef

Cheng F, Liu C, Jiang J, Lu W, Li W, Liu G, Zhou W, Huang J, Tang Y (2012) Prediction of drug-target interactions and drug repositioning via network-based inference. PLoS Comput Biol 8(5):e1002503PubMedCentralPubMedCrossRef

10.

Chuang H-Y, Lee E, Liu Y-T, Lee D, Ideker T (2007) Network-based classification of breast cancer metastasis. Mol Syst Biol 3(1):140PubMedCentralPubMed

11.

Barrett T, Suzek TO, Troup DB, Wilhite SE, Ngau W-C, Ledoux P, Rudnev D, Lash AE, Fujibuchi W, Edgar R (2005) NCBI GEO: mining millions of expression profiles—database and tools. Nucleic Acids Res 33(suppl 1):D562–D566PubMedCentralPubMed

12.

Pau Ni IB, Zakaria Z, Muhammad R, Abdullah N, Ibrahim N, Aina Emran N, Hisham Abdullah N, Syed Hussain SNA (2010) Gene expression patterns distinguish breast carcinomas from normal breast tissues: the Malaysian context. Pathol Res Pract 206(4):223–228PubMedCrossRef

13.

Karolchik D, Hinrichs AS, Kent WJ (2011) The UCSC genome browser. Curr Protoc Hum Genet: 18. 16. 11–18. 16. 33

14.

Larsson O, Wahlestedt C, Timmons JA (2005) Considerations when using the significance analysis of microarrays (SAM) algorithm. BMC Bioinformatics 6(1):129PubMedCentralPubMedCrossRef

15.

Butte AJ, Kohane IS (2000) Mutual information relevance networks: functional genomic clustering using pairwise entropy measurements. In: Pac Symp Biocomput. pp 418–429

16.

Faith JJ, Hayete B, Thaden JT, Mogno I, Wierzbowski J, Cottarel G, Kasif S, Collins JJ, Gardner TS (2007) Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles. PLoS Biol 5(1):e8PubMedCentralPubMedCrossRef

17.

Margolin AA, Nemenman I, Basso K, Wiggins C, Stolovitzky G, Favera RD, Califano A (2006) ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context. BMC Bioinformatics 7(Suppl 1):S7PubMedCentralPubMedCrossRef

18.

Langfelder P, Horvath S (2008) WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9(1):559PubMedCentralPubMedCrossRef

19.

D’haeseleer P, Liang S, Somogyi R (2000) Genetic network inference: from co-expression clustering to reverse engineering. Bioinformatics 16(8):707–726PubMedCrossRef

20.

Irrthum A, Wehenkel L, Geurts P (2010) Inferring regulatory networks from expression data using tree-based methods. PLoS One 5(9):e12776PubMedCentralPubMedCrossRef

21.

De Jong H (2002) Modeling and simulation of genetic regulatory systems: a literature review. J Comput Biol 9(1):67–103PubMedCrossRef

22.

Smoot ME, Ono K, Ruscheinski J, Wang P-L, Ideker T (2011) Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27(3):431–432PubMedCentralPubMedCrossRef

23.

Ahmed J, Meinel T, Dunkel M, Murgueitio MS, Adams R, Blasse C, Eckert A, Preissner S, Preissner R (2011) CancerResource: a comprehensive database of cancer-relevant proteins and compound interactions supported by experimental knowledge. Nucleic Acids Res 39(suppl 1):D960–D967PubMedCentralPubMedCrossRef

24.

Verdoodt B, Vogt M, Schmitz I, Liffers S-T, Tannapfel A, Mirmohammadsadegh A (2012) Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species. PLoS One 7(9):e44132PubMedCentralPubMedCrossRef

25.

Zhao D-D, Zhu Z-Y, Zhang C-F (2007) Advance in the development of target medicines for treatment of breast cancer. China Trop Med 4:70

26.

Bentrem D, Gaiha P, Jordan V (2003) Oestrogens, oestrogen receptors and breast cancer. Eur J Cancer Suppl 1(1):1–12CrossRef

27.

Tonon G (2008) From oncogene to network addiction: the new frontier of cancer genomics and therapeutics. Future Oncol 4(4):569–577PubMedCrossRef

28.

Ahmad F, Deris S, Othman N (2012) The inference of breast cancer metastasis through gene regulatory networks. J Biomed Inform 45(2):350–362PubMedCrossRef

29.

Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138(4):645–659PubMedCrossRef

30.

Fuchs D, Heinold A, Opelz G, Daniel V, Naujokat C (2009) Salinomycin induces apoptosis and overcomes apoptosis resistance in human cancer cells. Biochem Biophys Res Commun 390(3):743–749PubMedCrossRef

31.

Demicheli R, Coradini D (2011) Gene regulatory networks: a new conceptual framework to analyse breast cancer behaviour. Ann Oncol 22(6):1259–1265PubMedCrossRef

32.

Baca-López K, Mayorga M, Hidalgo-Miranda A, Gutiérrez-Nájera N, Hernández-Lemus E (2012) The role of master regulators in the metabolic/transcriptional coupling in breast carcinomas. PLoS One 7(8):e42678PubMedCentralPubMedCrossRef

Titel: Construction of breast cancer gene regulatory networks and drug target optimization
verfasst von: Yishan Xie
Rui Wang
Jian Zhu
Publikationsdatum: 01.10.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Archives of Gynecology and Obstetrics / Ausgabe 4/2014
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-014-3264-y

Neu im Fachgebiet Gynäkologie und Geburtshilfe

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Springer Medizin

Construction of breast cancer gene regulatory networks and drug target optimization

Abstract

Objective

Methods

Results

Conclusion

Neu im Fachgebiet Gynäkologie und Geburtshilfe

ICI-Therapie in der Schwangerschaft wird gut toleriert

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

Bei RSV-Impfung vor 60. Lebensjahr über Off-Label-Gebrauch aufklären!

Harnwegsinfektprophylaxe: Es geht auch ohne Antibiotika

Update Gynäkologie

Springer Medizin

Abstract

Objective

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2014

Patients with high-risk pregnancies and complicated deliveries have an increased risk of maternal postpartum readmissions

Does Cabergoline help in decreasing endometrioma size compared to LHRH agonist? A prospective randomized study

MiR-1246 promotes SiHa cervical cancer cell proliferation, invasion, and migration through suppression of its target gene thrombospondin 2

Gestational diabetes mellitus in twin pregnancies is not associated with adverse perinatal outcomes

Does minor trauma in pregnancy affect perinatal outcome?

Comparison of improved laparoscopic peritoneal vaginoplasty and gasless laparoscopic ileal vaginoplasty in treatment of androgen insensitivity syndrome

Neu im Fachgebiet Gynäkologie und Geburtshilfe

ICI-Therapie in der Schwangerschaft wird gut toleriert

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

Bei RSV-Impfung vor 60. Lebensjahr über Off-Label-Gebrauch aufklären!

Harnwegsinfektprophylaxe: Es geht auch ohne Antibiotika

Update Gynäkologie