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BMC Bioinformatics

Open Access

Transcriptome profile of OVCAR3 cisplatin-resistant ovarian cancer cell line

  • Shruti S Sakhare1,
  • Gautam G Rao2,
  • Sammed N Mandape1 and
  • Siddharth Pratap1Email author
Contributed equally
BMC Bioinformatics201415(Suppl 10):P21

https://doi.org/10.1186/1471-2105-15-S10-P21

Published: 29 September 2014

Background

The NIH:OVCAR-3 is a cisplatin refractory cell line established from malignant ascites of a patient with progressive adenocarcinoma of the ovary after combination chemotherapy with cyclophosphamide, Adriamycin, and cisplatin [1]. Thus, OVCAR3 serves as a model cell line for drug resistance in ovarian cancer. Here, we perform a comparative transcriptome analysis from the US National Cancer Institute human tumor cell line anticancer drug screen (NCI60) dataset [2]. Our results indicate a specific gene transcription profile of OVCAR3 genes relative to non-cancerous Human Ovarian Surface Epithelial cells (HOSE) and drug sensitive Serous Ovarian Cancer Epithelial Samples (CEPI) and SKOV3 cell lines. Pathway enrichment analysis from OVCAR3 unique transcripts was conducted using KEGG; Disease and Drug term enrichment used the PharmGKB [3] databases.

Materials and methods

Datasets from the NCI60 were obtained from the Gene Expression Omnibus (GEO) of NCBI [4] (OVCAR3 and SKOV3 from series GSE2003, OSE and CEPI from series GDS3592 and GSE14407). Transcriptome data analysis was conducted with Partek Genomics Suite version 6.6. The WEB-based GEne SeT AnaLysis Toolkit (WebGestalt) was used to perform enrichment analysis [5]. Genes present in KEGG pathway, PharmGKB Disease, and Drug terms enrichment sets were connected and expanded to one degree of biological interaction using the Michigan Molecular Interactions databases plugin [6] and visualized using Cytoscape version 2.8.3 [7].

Results

Transcriptome analysis of OVCAR3 specific gene expression changes resulted in 160 significant transcripts with a fold change > ±2 and an ANOVA derived Benjamini Hochberg adjusted p-value < 0.001. Enrichment analysis using a Hypergeometric test identified 189 PharmGKB Disease terms, 90 Drug terms and 31 KEGG pathways associated with these genes. A union of the disease, drug and KEGG pathway gene lists yielded 14 common genes for the dataset which were unique to OVCAR3 cells versus SKOV3 and CEPI (Table 1).
Table 1

Transcripts differentially expressed in OVCAR3 versus SKOV3 and CEPI having significant enrichment scores in KEGG Pathway, PharmGKB Drug and Disease databases.

Gene Symbol

Gene Name

Ensembl

ABCC4

ATP-binding cassette, sub-family C (CFTR/MRP), member 4

ENSG00000125257

AKR1C2

aldo-keto reductase family 1, member C2 (dihydrodiol dehydrogenase 2; bile acid binding protein; 3-alpha hydroxysteroid dehydrogenase, type III)

ENSG00000151632

MLH1

mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)

ENSG00000076242

GLS

glutaminase

ENSG00000115419

ITGA3

integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3 receptor)

ENSG00000005884

UGT1A6

UDP glucuronosyltransferase 1 family, polypeptide A6

ENSG00000167165

PPARG

peroxisome proliferator-activated receptor gamma

ENSG00000132170

NNMT

nicotinamide N-methyltransferase

ENSG00000166741

PTGIS

prostaglandin I2 (prostacyclin) synthase

ENSG00000124212

ABCC3

ATP-binding cassette, sub-family C (CFTR/MRP), member 3

ENSG00000108846

UGT1A1

UDP glucuronosyltransferase 1 family, polypeptide A1

ENSG00000241635

ERBB2

v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)

ENSG00000141736

AKR1C1

aldo-keto reductase family 1, member C1 (dihydrodiol dehydrogenase 1; 20-alpha (3-alpha)-hydroxysteroid dehydrogenase)

ENSG00000187134

FGF2

fibroblast growth factor 2 (basic)

ENSG00000138685

Conclusions

This list of OVCAR3 unique genes, and the resulting interactions graph (Figure 1) represent potential pathways of drug resistance associated genes in ovarian cancer. Notably, ERBB2 (HER2) and FYN are the hub genes of the interaction network specific for OVCAR3 cell line. Thus, they may provide valuable insights into the drug resistance etiology of ovarian cancer. ERBB2 (HER2) has previously been reported to interact with Estrogen Receptor (ESR2) in Breast Cancer [8] and FYN has been implicated in Glioblastoma and T-cell Lymphomas [9, 10]; however their detailed roles in Ovarian Cancer have only recently been studied, warranting further investigation [11, 12].
Figure 1

Interaction network of OVCAR3 unique genes. Diamond and rectangle nodes are seed nodes of 14 OVCAR3 unique genes; circular nodes are 1 degree of biological interactions; rounded rectangular nodes are the highly connected hubs in the network (FYN and ERBB2).

Notes

Declarations

Acknowledgements

Funding provided by NIH grants MD007586 and MD007593 from the National Institute on Minority Health and Health Disparities (NIMHD).

Authors’ Affiliations

(1)
Bioinformatics Core, Meharry Medical College
(2)
Obstetrics, Gynecology and Reproductive Sciences, University of Maryland

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Copyright

© Sakhare et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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