The Expression and Role Analysis of Methylation-Regulated Differentially Expressed Gene UBE2C in Pan-Cancer, Especially for HGSOC

SIMPLE SUMMARY: DNA methylation has attracted a great deal of scientific interest as an early biomarker and potential therapeutic target. HGSOC result in high mortality due to the absence of reliable biomarkers for early diagnosis and prognosis. In this study, we performed an integrated bioinformatic analysis and found that UBE2C was hypomethylation and overexpression in ovarian cancer, which was associated with advanced cancer stages and poor prognoses. Meantime, this finding was also confirmed in pan-cancer analysis. Furthermore, the experimental validation of the expression and role of UBE2C was performed on HGSOC tissues and cancer cell lines. Importantly, demethylation could upregulate the expression of UBE2C. Taken together, methylation-regulated UBE2C may be a novel biomarker for diagnosis and prognosis, not only for ovarian cancer but a variety of cancers. ABSTRACT: High-grade serous ovarian cancer (HGSOC) is the most fatal gynecological malignant tumor. DNA methylation is associated with the occurrence and development of a variety of tumor types, including HGSOC. However, the signatures regarding DNA methylation changes for HGSOC diagnosis and prognosis are less explored. Here, we screened differentially methylated genes and differentially expressed genes in HGSOC through the GEO database. We identified that UBE2C was hypomethylation and overexpression in ovarian cancer, which was associated with more advanced cancer stages and poor prognoses. Additionally, the pan-cancer analysis showed that UBE2C was overexpressed and hypomethylation in almost all cancer types and was related to poor prognoses for various cancers. Next, we established a risk or prognosis model related to UBE2C methylation sites and screened out the three sites (cg03969725, cg02838589, and cg00242976). Furthermore, we experimentally validated the overexpression of UBE2C in HGSOC clinical samples and ovarian cell lines using quantitative real-time PCR, Western blot, and immunohistochemistry. Importantly, we discovered that ovarian cancer cell lines had lower DNA methylation levels of UBE2C than IOSE-80 cells (normal ovarian epithelial cell line) by bisulfite sequencing PCR. Consistently, treatment with 5-Azacytidine (a methylation inhibitor) was able to restore the expression of UBE2C. Taken together, our study may help us to understand the underlying molecular mechanism of UBE2C in pan-cancer tumorigenesis; it may be a useful biomarker for diagnosis, treatment, and monitoring, not only of ovarian cancer but a variety of cancers.