Expression Profiling Identifies Genes Involved in Neoplastic Transformation of Serous Ovarian Cancer

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2009 Oct 24

PMID 19849863

Citations 24

Authors

Melissa A Merritt

Peter G Parsons

Tanya R Newton

Adam C Martyn

Penelope M Webb

Adele C Green

David J Papadimos

Glen M Boyle

Affiliations

Soon will be listed here.

Abstract

Background: The malignant potential of serous ovarian tumors, the most common ovarian tumor subtype, varies from benign to low malignant potential (LMP) tumors to frankly invasive cancers. Given the uncertainty about the relationship between these different forms, we compared their patterns of gene expression.

Methods: Expression profiling was carried out on samples of 7 benign, 7 LMP and 28 invasive (moderate and poorly differentiated) serous tumors and four whole normal ovaries using oligonucleotide microarrays representing over 21,000 genes.

Results: We identified 311 transcripts that distinguished invasive from benign tumors, and 20 transcripts that were significantly differentially expressed between invasive and LMP tumors at p < 0.01 (with multiple testing correction). Five genes that were differentially expressed between invasive and either benign or normal tissues were validated by real time PCR in an independent panel of 46 serous tumors (4 benign, 7 LMP, 35 invasive). Overexpression of SLPI and WNT7A and down-regulation of C6orf31, PDGFRA and GLTSCR2 were measured in invasive and LMP compared with benign and normal tissues. Over-expression of WNT7A in an ovarian cancer cell line led to increased migration and invasive capacity.

Conclusion: These results highlight several genes that may play an important role across the spectrum of serous ovarian tumorigenesis.

Citing Articles

Identification of lncRNAs Deregulated in Epithelial Ovarian Cancer Based on a Gene Expression Profiling Meta-Analysis.

Salamini-Montemurri M, Lamas-Maceiras M, Lorenzo-Catoira L, Vizoso-Vazquez A, Barreiro-Alonso A, Rodriguez-Belmonte E Int J Mol Sci. 2023; 24(13).

PMID: 37445988 PMC: 10341812. DOI: 10.3390/ijms241310798.

Accuracy of CCL20 expression level as a liquid biopsy-based diagnostic biomarker for ovarian carcinoma.

Sakares W, Wongkhattiya W, Vichayachaipat P, Chaiwut C, Yodsurang V, Nutthachote P Front Oncol. 2022; 12:1038835.

PMID: 36387204 PMC: 9647055. DOI: 10.3389/fonc.2022.1038835.

Ovarian Cancer: Biomarkers and Targeted Therapy.

Radu M, Pradatu A, Duica F, Micu R, Cretoiu S, Suciu N Biomedicines. 2021; 9(6).

PMID: 34207450 PMC: 8235073. DOI: 10.3390/biomedicines9060693.

Meta-analysis based gene expression profiling reveals functional genes in ovarian cancer.

Zhao L, Li Y, Zhang Z, Zou J, Li J, Wei R Biosci Rep. 2020; 40(11).

PMID: 33135729 PMC: 7677829. DOI: 10.1042/BSR20202911.

Role of Autophagy in Cancer Cell Response to Nucleolar and Endoplasmic Reticulum Stress.

Pecoraro A, Pagano M, Russo G, Russo A Int J Mol Sci. 2020; 21(19).

PMID: 33020404 PMC: 7582989. DOI: 10.3390/ijms21197334.

References

Gilks C, Vanderhyden B, Zhu S, van de Rijn M, Longacre T . Distinction between serous tumors of low malignant potential and serous carcinomas based on global mRNA expression profiling. Gynecol Oncol. 2005; 96(3):684-94. DOI: 10.1016/j.ygyno.2004.11.039. View

Jazaeri A, Yee C, Sotiriou C, Brantley K, Boyd J, Liu E . Gene expression profiles of BRCA1-linked, BRCA2-linked, and sporadic ovarian cancers. J Natl Cancer Inst. 2002; 94(13):990-1000. DOI: 10.1093/jnci/94.13.990. View

Shridhar V, Lee J, Pandita A, ITURRIA S, Avula R, Staub J . Genetic analysis of early- versus late-stage ovarian tumors. Cancer Res. 2001; 61(15):5895-904. View

Hochberg Y, Benjamini Y . More powerful procedures for multiple significance testing. Stat Med. 1990; 9(7):811-8. DOI: 10.1002/sim.4780090710. View

Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D . New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst. 1990; 82(13):1107-12. DOI: 10.1093/jnci/82.13.1107. View

Pavey S, Johansson P, Packer L, Taylor J, Stark M, Pollock P . Microarray expression profiling in melanoma reveals a BRAF mutation signature. Oncogene. 2004; 23(23):4060-7. DOI: 10.1038/sj.onc.1207563. View

Sieben N, Oosting J, Flanagan A, Prat J, Roemen G, Kolkman-Uljee S . Differential gene expression in ovarian tumors reveals Dusp 4 and Serpina 5 as key regulators for benign behavior of serous borderline tumors. J Clin Oncol. 2005; 23(29):7257-64. DOI: 10.1200/JCO.2005.02.2541. View

Mills G, Lu Y, Fang X, Wang H, Eder A, Mao M . The role of genetic abnormalities of PTEN and the phosphatidylinositol 3-kinase pathway in breast and ovarian tumorigenesis, prognosis, and therapy. Semin Oncol. 2001; 28(5 Suppl 16):125-41. DOI: 10.1016/s0093-7754(01)90290-8. View

Meinhold-Heerlein I, Bauerschlag D, Hilpert F, Dimitrov P, Sapinoso L, Orlowska-Volk M . Molecular and prognostic distinction between serous ovarian carcinomas of varying grade and malignant potential. Oncogene. 2004; 24(6):1053-65. DOI: 10.1038/sj.onc.1208298. View

10.

Shih I, Kurman R . Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004; 164(5):1511-8. PMC: 1615664. DOI: 10.1016/s0002-9440(10)63708-x. View

11.

Okahara F, Ikawa H, Kanaho Y, Maehama T . Regulation of PTEN phosphorylation and stability by a tumor suppressor candidate protein. J Biol Chem. 2004; 279(44):45300-3. DOI: 10.1074/jbc.C400377200. View

12.

Matei D, Graeber T, Baldwin R, Karlan B, Rao J, Chang D . Gene expression in epithelial ovarian carcinoma. Oncogene. 2002; 21(41):6289-98. DOI: 10.1038/sj.onc.1205785. View

13.

Biade S, Marinucci M, Schick J, Roberts D, Workman G, Sage E . Gene expression profiling of human ovarian tumours. Br J Cancer. 2006; 95(8):1092-100. PMC: 2360705. DOI: 10.1038/sj.bjc.6603346. View

14.

Lee C, Shvartsman H, Deavers M, Wang S, Xia W, Schmandt R . beta-catenin nuclear localization is associated with grade in ovarian serous carcinoma. Gynecol Oncol. 2003; 88(3):363-8. DOI: 10.1016/s0090-8258(02)00015-x. View

15.

Drapkin R, Crum C, Hecht J . Expression of candidate tumor markers in ovarian carcinoma and benign ovary: evidence for a link between epithelial phenotype and neoplasia. Hum Pathol. 2004; 35(8):1014-21. DOI: 10.1016/j.humpath.2004.04.014. View

16.

Taipale J, Beachy P . The Hedgehog and Wnt signalling pathways in cancer. Nature. 2001; 411(6835):349-54. DOI: 10.1038/35077219. View

17.

Drapkin R, von Horsten H, Lin Y, C Mok S, Crum C, Welch W . Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005; 65(6):2162-9. DOI: 10.1158/0008-5472.CAN-04-3924. View

18.

Calvo R, West J, Franklin W, Erickson P, Bemis L, Li E . Altered HOX and WNT7A expression in human lung cancer. Proc Natl Acad Sci U S A. 2000; 97(23):12776-81. PMC: 18840. DOI: 10.1073/pnas.97.23.12776. View

19.

Donninger H, Bonome T, Radonovich M, Pise-Masison C, Brady J, Shih J . Whole genome expression profiling of advance stage papillary serous ovarian cancer reveals activated pathways. Oncogene. 2004; 23(49):8065-77. DOI: 10.1038/sj.onc.1207959. View

20.

Chen V, Ruiz B, Killeen J, Cote T, Wu X, Correa C . Pathology and classification of ovarian tumors. Cancer. 2003; 97(10 Suppl):2631-42. DOI: 10.1002/cncr.11345. View