Abstract
ObjectiveThe aim of the present study was to construct and test a liquid-liquid phase separation (LLPS)-related gene signature as a prognostic tool for epithelial ovarian cancer (EOC).Materials and MethodsThe data set GSE26712 was used to screen the differentially expressed LLPS-related genes. Functional enrichment analysis was performed to reveal the potential biological functions. GSE17260 and GSE32062 were combined as the discovery to construct an LLPS-related gene signature through a three-step analysis (univariate Cox, least absolute shrinkage and selection operator, and multivariate Cox analyses). The EOC data set from The Cancer Genome Atlas as the test set was used to test the LLPS-related gene signature.ResultsThe differentially expressed LLPS-related genes involved in several cancer-related pathways, such as MAPK signaling pathway, cell cycle, and DNA replication. Eleven genes were selected to construct the LLPS-related gene signature risk index as prognostic biomarker for EOC. The risk index could successfully divide patients with EOC into high- and low-risk groups. The patients in high-risk group had significantly shorter overall survival than those with in low-risk group. The LLPS-related gene signature was validated in the test set and may be an independent prognostic factor compared to routine clinical features.ConclusionWe constructed and validated an LLPS-related gene signature as a prognosis tool in EOC through integrated analysis of multiple data sets.
Highlights
Rapid progress was made in recent decades in identifying the genetic causes of cancers, our mechanistic understanding of these diseases remains incomplete and limits our ability to provide effective treatments
Multiple liquid-liquid phase separation (LLPS)-Related Genes Aberrantly Expressed in Epithelial ovarian cancer (EOC)
PhaSepDB database includes 2957 eligible genes, a total of 1767 LLPS-related genes were found in the GSE26712, among them, 252 genes were down-regulated and 248 were up-regulated in EOC compared to the normal ovarian surface epithelium (Figure S1A)
Summary
Rapid progress was made in recent decades in identifying the genetic causes of cancers, our mechanistic understanding of these diseases remains incomplete and limits our ability to provide effective treatments. The emerging evidence indicated that aberrant forms of LLPS are associated with many human diseases, including cancer [7]. The FET protein family is involved in phase transitions at sites of RNA storage [8, 9] and assembles into higher-order structures by a process that is stimulated by RNA [10, 11]. These functions are often impaired in human diseases, such as cancer and neurodegenerative diseases [12, 13]
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