Genomic markers of ovarian adenocarcinoma and its relevancy to the effectiveness of chemotherapy

Englert‑Golon,Monika; Burchardt,Bartosz; Budny,Bartlomiej; Dębicki,Szymon; Majchrzycka,Blanka; Wrotkowska,Elzbieta; Jasiński,Piotr; Ziemnicka,Katarzyna; Słopień,Radosław; Ruchała,Marek; Sajdak,Stefan

doi:10.3892/ol.2017.6590

Genomic markers of ovarian adenocarcinoma and its relevancy to the effectiveness of chemotherapy

Authors:
- Monika Englert‑Golon
- Bartosz Burchardt
- Bartlomiej Budny
- Szymon Dębicki
- Blanka Majchrzycka
- Elzbieta Wrotkowska
- Piotr Jasiński
- Katarzyna Ziemnicka
- Radosław Słopień
- Marek Ruchała
- Stefan Sajdak
View Affiliations

Affiliations: Surgical Gynecology Clinic of The Gynecological and Obstetrics Clinical Hospital, Poznan University of Medical Sciences, 60‑535 Poznan, Poland, Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, 60‑535 Poznan, Poland, Gynecological and Obstetrics Clinical Hospital, Poznan University of Medical Sciences, 60‑535 Poznan, Poland, Department of Gynecological Endocrinology, Poznan University of Medical Sciences, 60‑535 Poznan, Poland
Published online on: July 17, 2017 https://doi.org/10.3892/ol.2017.6590
Pages: 3401-3414
Copyright: © Englert‑Golon et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Ovarian cancer is the eighth most common cancer and the seventh highest cause of cancer‑associated mortality in women worldwide. It is the second highest cause of mortality among female reproductive malignancies. The current standard first‑line treatment for advanced ovarian cancer includes a combination of surgical debulking and standard systemic platinum‑based chemotherapy with carboplatin and paclitaxel. Although a deeper understanding of this disease has been attained, relapse occurs in 70% of patients 18 months subsequent to the first‑line treatment. Therefore, it is crucial to develop a novel drug that effectively affects ovarian cancer, particularly tumors that are resistant to current chemotherapy. The aim of the present study was to identify genes whose expression may be used to predict survival time or prognosis in ovarian cancer patients treated with chemotherapy. Gene or protein expression is an important issue in chemoresistance and survival prediction in ovarian cancer. In the present study, the research group consisted of patients treated at the Surgical Clinic of the Gynecology and Obstetrics Gynecological Clinical Hospital, Poznan University of Medical Sciences (Poznan, Poland) between May 2006 and November 2014. Additional eligibility criteria were a similar severity (International Federation of Gynecolgy and Obstetrics stage III) at the time of diagnosis, treatment undertaken in accordance with the same schedule, and an extremely good response to treatment or a lack of response to treatment. The performance of the OncoScan® assay was evaluated by running the assay on samples obtained from the four patients and by following the recommended protocol outlined in the OncoScan assay manual. The genomic screening using Affymetrix OncoScan Arrays resulted in the identification of large genomic rearrangements across all cancer tissues. In general, chromosome number changes were detected in all examined tissues. The OncoScan arrays enabled the identification of ~100 common somatic mutations. Chemotherapy response in ovarian cancer is extremely complex and challenging to study. The present study identified specific genetic alterations associated with ovarian cancer, but not with response for treatment.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
3	Potrykowska A, Strzelecki Z, Szymborski J and Witkowski J: Cancer incidence and mortality versus the demographic situation of PolandRządowa Rada Ludnościowa. Warsaw: pp. 117–130. 2014, (In Polish).
4	Paik ES, Lee YY, Lee EJ, Choi CH, Kim TJ, Lee JW, Bae DS and Kim BG: Survival analysis of revised 2013 FIGO staging classification of epithelial ovarian cancer and comparison with previous FIGO staging classification. Obstet Gynecol Sci. 58:124–134. 2015. View Article : Google Scholar : PubMed/NCBI
5	Suh DH, Kim TH, Kim JW, Kim SY, Kim HS, Lee TS, Chung HH, Kim YB, Park NH and Song YS: Improvements to the FIGO staging for ovarian cancer: Reconsideration of lymphatic spread and intraoperative tumor rupture. J Gynecol Oncol. 24:352–358. 2013. View Article : Google Scholar : PubMed/NCBI
6	van der Burg ME, van Lent M, Buyse M, Kobierska A, Colombo N, Favalli G, Lacave AJ, Nardi M, Renard J and Pecorelli S: The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological cancer cooperative group of the European Organization for research and treatment of cancer. N Engl J Med. 332:629–634. 1995. View Article : Google Scholar : PubMed/NCBI
7	Raja FA, Chopra N and Ledermann JA: Optimal first-line treatment in ovarian cancer. Ann Oncol. 23:(Suppl 10). x118–x127. 2012. View Article : Google Scholar : PubMed/NCBI
8	Lloyd KL, Cree IA and Savage RS: Prediction of resistance to chemotherapy in ovarian cancer: A systematic review. BMC Cancer. 15:1172015. View Article : Google Scholar : PubMed/NCBI
9	Pliarchopoulou K and Pectasides D: Epithelial ovarian cancer: Focus on targeted therapy. Crit Rev Oncol Hematol. 79:17–23. 2011. View Article : Google Scholar : PubMed/NCBI
10	Zhu LC, Gao J, Hu ZH, Schwab CL, Zhuang HY, Tan MZ, Yan LM, Liu JJ, Zhang DY and Lin B: Membranous expressions of Lewis y and CAM-DR-related markers are independent factors of chemotherapy resistance and poor prognosis in epithelial ovarian cancer. Am J Cancer Res. 5:830–843. 2015.PubMed/NCBI
11	Vinogradov S and Wei X: Cancer stem cells and drug resistance: The potential of nanomedicine. Nanomedicine (Lond). 7:597–615. 2012. View Article : Google Scholar : PubMed/NCBI
12	Markman M and Bookman MA: Second-line treatment of ovarian cancer. Oncologist. 5:26–35. 2000. View Article : Google Scholar : PubMed/NCBI
13	Cooley M, Fang P, Fang F, Nephew KP and Chien J: Molecular determinants of chemotherapy resistance in ovarian cancer. Pharmacogenomics. 16:1763–1767. 2015. View Article : Google Scholar : PubMed/NCBI
14	Foster JM, Oumie A, Togneri FS, Vasques FR, Hau D, Taylor M, Tinkler-Hundal E, Southward K, Medlow P, McGreeghan-Crosby K, et al: Cross-laboratory validation of the OncoScan^® FFPE Assay, a multiplex tool for whole genome tumour profiling. BMC Med Genomics. 8:52015. View Article : Google Scholar : PubMed/NCBI
15	Bast RC Jr, Hennessy B and Mills GB: The biology of ovarian cancer: New opportunities for translation. Nat Rev Cancer. 9:415–428. 2009. View Article : Google Scholar : PubMed/NCBI
16	Musrap N, Tuccitto A, Karagiannis GS, Saraon P, Batruch I and Diamandis EP: Comparative proteomics of ovarian cancer aggregate formation reveals an increased expression of calcium-activated chloride channel regulator 1 (CLCA1). J Biol Chem. 290:17218–17227. 2015. View Article : Google Scholar : PubMed/NCBI
17	Burleson KM, Casey RC, Skubitz KM, Pambuccian SE, Oegema TR Jr and Skubitz AP: Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecol Oncol. 93:170–181. 2004. View Article : Google Scholar : PubMed/NCBI
18	Høgdall E: Cancer antigen 125 and prognosis. Curr Opin Obstet Gynecol. 20:4–8. 2008. View Article : Google Scholar : PubMed/NCBI
19	Gadducci A, Cosio S, Fanucchi A, Negri S, Cristofani R and Genazzani AR: The predictive and prognostic value of serum CA 125 half-life during paclitaxel/platinum-based chemotherapy in patients with advanced ovarian carcinoma. Gynecol Oncol. 93:131–136. 2004. View Article : Google Scholar : PubMed/NCBI
20	Menon U, Skates SJ, Lewis S, Rosenthal AN, Rufford B, Sibley K, Macdonald N, Dawnay A, Jeyarajah A, Bast RC Jr, et al: Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer. J Clin Oncol. 23:7919–7926. 2005. View Article : Google Scholar : PubMed/NCBI
21	Hasanbegovic L, Alicelebic S and Sljivo N: Comparison of specific ovarian tumor markers by elecsys analyzer 2010. Acta Inform Med. 23:86–89. 2015. View Article : Google Scholar : PubMed/NCBI
22	Hellström I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, Drescher C, Urban N and Hellström KE: The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 63:3695–3700. 2003.PubMed/NCBI
23	Moore RG, MacLaughlan S and Bast RC Jr: Current state of biomarker development for clinical application in epithelial ovarian cancer. Gynecol Oncol. 116:240–245. 2010. View Article : Google Scholar : PubMed/NCBI
24	Huhtinen K, Suvitie P, Hiissa J, Junnila J, Huvila J, Kujari H, Setälä M, Härkki P, Jalkanen J, Fraser J, et al: Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer. 100:1315–1319. 2009. View Article : Google Scholar : PubMed/NCBI
25	Moore RG, Miller MC, Steinhoff MM, Skates SJ, Lu KH, Lambert-Messerlian G and Bast RC Jr: Serum HE4 levels are less frequently elevated than CA125 in women with benign gynecologic disorders. Am J Obstet Gynecol. 206(351): e1–8. 2012.
26	Górski B, Byrski T, Huzarski T, Jakubowska A, Menkiszak J, Gronwald J, Pluzańska A, Bebenek M, Fischer-Maliszewska L, Grzybowska E, et al: Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer. Am J Hum Genet. 66:1963–1968. 2000. View Article : Google Scholar : PubMed/NCBI
27	Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP, Markowitz S, Willson JK, Hamilton SR, Kinzler KW, et al: Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci USA. 95:6870–6875. 1998. View Article : Google Scholar : PubMed/NCBI
28	Curia MC, Palmirotta R, Aceto G, Messerini L, Verì MC, Crognale S, Valanzano R, Ficari F, Fracasso P, Stigliano V, et al: Unbalanced germ-line expression of hMLH1 and hMSH2 alleles in hereditary nonpolyposis colorectal cancer. Cancer Res. 59:3570–3575. 1999.PubMed/NCBI
29	Debniak T, Kurzawski G, Gorski B, Kladny J, Domagala W and Lubinski J: Value of pedigree/clinical data, immunohistochemistry and microsatellite instability analyses in reducing the cost of determining hMLH1 and hMSH2 gene mutations in patients with colorectal cancer. Eur J Cancer. 36:49–54. 2000. View Article : Google Scholar : PubMed/NCBI
30	Ali AY, Farrand L, Kim JY, Byun S, Suh JY, Lee HJ and Tsang BK: Molecular determinants of ovarian cancer chemoresistance: New insights into an old conundrum. Ann N Y Acad Sci. 1271:58–67. 2012. View Article : Google Scholar : PubMed/NCBI
31	Thibault B, Castells M, Delord JP and Couderc B: Ovarian cancer microenvironment: Implications for cancer dissemination and chemoresistance acquisition. Cancer Metastasis Rev. 33:17–39. 2014. View Article : Google Scholar : PubMed/NCBI
32	Li M, Yin J, Mao N and Pan L: Upregulation of phosphorylated cofilin 1 correlates with taxol resistance in human ovarian cancer in vitro and in vivo. Oncol Rep. 29:58–66. 2013.PubMed/NCBI
33	Mok SC, Bonome T, Vathipadiekal V, Bell A, Johnson ME, Wong KK, Park DC, Hao K, Yip DK, Donninger H, et al: A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: Microfibril-associated glycoprotein 2. Cancer Cell. 16:521–532. 2009. View Article : Google Scholar : PubMed/NCBI
34	Fullwood P, Marchini S, Rader JS, Martinez A, Macartney D, Broggini M, Morelli C, Barbanti-Brodano G, Maher ER and Latif F: Detailed genetic and physical mapping of tumor suppressor loci on chromosome 3p in ovarian cancer. Cancer Res. 59:4662–4667. 1999.PubMed/NCBI
35	Chng HW, Camplejohn RS, Stone MG, Hart IR and Nicholson LJ: A new role for the anti-apoptotic gene A20 in angiogenesis. Exp Cell Res. 312:2897–2907. 2006. View Article : Google Scholar : PubMed/NCBI
36	Shridhar V, Staub J, Huntley B, Cliby W, Jenkins R, Pass HI, Hartmann L and Smith DI: A novel region of deletion on chromosome 6q23.3 spanning less than 500 Kb in high grade invasive epithelial ovarian cancer. Oncogene. 18:3913–3918. 1999. View Article : Google Scholar : PubMed/NCBI
37	Shayesteh L, Lu Y, Kuo WL, Baldocchi R, Godfrey T, Collins C, Pinkel D, Powell B, Mills GB and Gray JW: PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet. 21:99–102. 1999. View Article : Google Scholar : PubMed/NCBI
38	Cheaib B, Auguste A and Leary A: The PI3K/Akt/mTOR pathway in ovarian cancer: Therapeutic opportunities and challenges. Chin J Cancer. 34:4–16. 2015. View Article : Google Scholar : PubMed/NCBI
39	Friedlander ML, Russell K, Millis S, Gatalica Z, Bender R and Voss A: Molecular profiling of clear cell ovarian cancers: Identifying potential treatment targets for clinical trials. Int J Gynecol Cancer. 26:648–654. 2016. View Article : Google Scholar : PubMed/NCBI