J Gynecol Oncol.
2023 Nov;34(6):e71. 10.3802/jgo.2023.34.e71.
Integrated analysis of DNA methylome and transcriptome reveals SFRP1 and LIPG as potential drivers of ovarian cancer metastasis
- Affiliations
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- 1Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
- 2Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Department of Gynecologic Oncology, Women’s Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
- 3Cancer Center, Zhejiang University, Hangzhou, China
- KMID: 2552657
- DOI: http://doi.org/10.3802/jgo.2023.34.e71
Abstract
Objective
More than 75% of ovarian cancer patients are diagnosed at advanced stages and die of tumor cell metastasis. This study aimed to identify new epigenetic and transcriptomic alterations associated with ovarian cancer metastasis.
Methods
Two cell sublines with low- and high-metastasis potentials were derived from the ovarian cancer cell line A2780. Genome-wide DNA methylome and transcriptome profiling were carried out in these two sublines by Reduced Representation Bisulfite Sequencing and RNA-seq technologies. Cell-based assays were conducted to support the clinical findings.
Results
There are distinct DNA methylation and gene expression patterns between the two cell sublines with low- and high-metastasis potentials. Integrated analysis identified 33 methylation-induced genes potentially involved in ovarian cancer metastasis. The DNA methylation patterns of two of them (i.e., SFRP1 and LIPG) were further validated in human specimens, indicating that they were hypermethylated and downregulated in peritoneal metastatic ovarian carcinoma compared to primary ovarian carcinoma. Patients with lower SFRP1 and LIPG expression tend to have a worse prognosis. Functionally, knockdown of SFRP1 and LIPG promoted cell growth and migration, whereas their overexpression resulted in the opposite effects. In particular, knockdown of SFRP1 could phosphorylate GSK3β and increase β-catenin expression, leading to deregulated activation of the Wnt/β-catenin signaling.
Conclusion
Many systemic and important epigenetic and transcriptomic alterations occur in the progression of ovarian cancer. In particular, epigenetic silencing of SFRP1 and LIPG is a potential driver event in ovarian cancer metastasis. They can be used as prognostic biomarkers and therapeutic targets for ovarian cancer patients.
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