The online version of this article (doi:10.1186/1757-2215-7-73) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
FR carried out MCA-RDA analysis to screen the differentially methylated genes and drafted the manuscript. DBW participated in the design of the study and performed the statistical analysis. TL carried out MSP. YHC carried out immunohistochemistry, YL participated in its design and helped to draft the manuscript. All authors read and approved the final manuscript.
Key roles for epigenetic mechanisms in tumorigenesis are well accepted, while the relationship between gene methylation and malignant transformation of ovarian endometriosis (EMS) was seldom reported. In this study, we aimed to screen for aberrantly methylated genes associated with the malignant transformation of ovarian EMS and to preliminarily verify the reliability of screened results by detecting the methylation status and protein expression of the candidate gene in a larger scale of formaldehyde-fixed and paraffin-embedded (FFPE) samples.
Methylated CpG island amplification coupled with representational difference analysis (MCA-RDA) was performed on 3 couples of endometriosis-associated ovarian carcinoma (EAOC) fresh samples to identify differentially methylated candidate genes related to malignant transformation of ovarian EMS; Methylation-specific PCR (MSP) and immunohistochemistry were performed in 30 EAOC samples to detected the methylation status and protein expression of RASSF2 gene to verify the reliability of MCA-RDA results.
Nine differentially methylated genes were obtained by MCA-RDA as candidate genes for malignant transformation of EMS; Methylation frequency of RASSF2 in the neoplastic tissues of EAOC group was higher than that in the ectopic endometria (p < 0.05). While protein expression of RASSF2 in the neoplastic tissues was lower than that in the ectopic endometria of the EAOC group (p < 0.05) Absence of protein expression of RASSF2 was significantly correlated with the promoter methylation of the gene (p < 0.05).
RASSF2, RUNX3, GSTZ1, CYP2A, GBGT1, NDUFS1, SPOCK2, ADAM22, and TRIM36 were candidate genes for malignant transformation of ovarian EMS and epigenetic inactivation of RASSF2 by promoter hypermethylation is an early event in malignant transformation of ovarian EMS. The screen results were reliable and worthy of further study.
Sampson JA: Endometrial carcinoma of the ovary, arising in endometrial tissue in that organ. Arch Surg 1925, 10: 1–72. CrossRef
Scott RB: Malignant changes in endometriosis. Obstet Gynecol 1925, 2: 283–289.
Jian-Feng W, Dong-Qiu D: Metastatic suppressor genes inactivated by aberrant methylation in gastric cancer. World J Gastroenterol 2007, 13: 5692–5698. CrossRef
Toyota M, Ho C, Ahuja N, Jair KW, Li Q, Ohe-Toyota M, Baylin SB, Issa JP: Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. Cancer Res 1999, 59: 2307–2312. PubMed
Ren F, Wang DB, Li T: Epigenetic inactivation of SPOCK2 in the malignant transformation of ovarian endometriosis. Zhonghua Fu Chan Ke Za Zhi 2011, 46(11):822–825. PubMed
Meyer JL, Zimbardi D, Podgaec S, Amorim RL, Abrão MS, Rainho CA: DNA methylation patterns of steroid receptor genes ESR1, ESR2 and PGR in deep endometriosis compromising the rectum. Int J Mol Med 2014, 33(4):897–904. PubMed
Lin K, Zhan H, Ma J, Xu K, Wu R, Zhou C, Lin J: Increased steroid receptor RNA activator protein (SRAP) accompanied by decreased estrogen receptor-beta (ER-β) levels during the malignant transformation of endometriosis associated ovarian clear cell carcinoma. Acta Histochem 2014, S0065–1281(14):00044.
Maruyama R, Akino K, Toyota M, Suzuki H, Imai T, Ohe-Toyota M, Yamamoto E, Nojima M, Fujikane T, Sasaki Y, Yamashita T, Watanabe Y, Hiratsuka H, Hirata K, Itoh F, Imai K, Shinomura Y, Tokino T: Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer. Carcinogenesis 2008, 29: 1312–1318. PubMedCentralCrossRefPubMed
- Identification of differentially methylated genes in the malignant transformation of ovarian endometriosis
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