Abstract
Ovarian cancer is the most common and aggressive type of tumor of the female reproductive system. Two factors account for this detrimental clinical presentation: (i) the lack of early detection methods and (ii) the inherently aggressive nature of this malignancy. Currently, transcriptomic analyses have become important tools to identify new targets in different cancer types. In this study, by measuring expression levels in ovarian cancer samples and stem cell samples, we identified 24 tumor suppressor genes consistently associated with poor prognosis. Combined results further revealed a potential therapeutic candidate, BTG2, which belongs to the antiproliferative gene family. Our results showed that BTG2 expression regulated ovarian cancer cell proliferation via G1/S phase cell cycle arrest by regulating Cyclin D1, CDK4, p-AKT, and p-ERK expression. BTG2 also inhibited cell migration by modulating MMP-2 and MMP-9 expression. Furthermore, xenograft models confirmed a growth inhibitory effect of BTG2 in ovarian cancer in vivo. BTG2 was significantly associated with ovarian cancer FIGO stage and grade in the clinic. Our findings indicated that BTG2 exerts a suppressive impact on ovarian cancer and could be a potential biomarker.
Highlights
Ovarian cancer is the leading and most common female reproductive malignancy among female patients, with 25,000 deaths per year in China alone [1]
Our results showed that phosphorylation levels of AKT and Extracellular regulated protein kinases (ERKs) were increased in shBTG2 group and decreased in GV-B cell translocation gene 2 (BTG2) group compared to the respective control groups
By comparing tumor samples to normal samples, we identified a set of 24 downregulated genes that affected patient survival
Summary
Ovarian cancer is the leading and most common female reproductive malignancy among female patients, with 25,000 deaths per year in China alone [1]. An improved understanding of the genetic and molecular heterogeneity among patients and identification of Therapeutic Target BTG2 in OV potential biomarkers to diagnose and monitor treatment for ovarian cancer at an earlier stage are urgently needed. Because novel therapeutic strategies based on these findings have not been developed, it is necessary to investigate additional pathways of gene deregulation in ovarian cancer. Traditional tumor cytoreductive surgery combined with cisplatin systemic chemotherapy has a certain effect on reducing tumor volume and alleviating clinical symptoms, but residual epithelial ovarian cancer stem cells after treatment can rebuild tumor tissue in a short time, which is the root cause of ovarian cancer recurrence and refractory [15].identifying regulators that maintain ovarian cancer stem cell phenotypes and/or contribute to their survival is critical for designing novel therapeutic strategies [16, 17]
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