Significance of liquid-liquid phase separation (LLPS)-related genes in breast cancer: a multi-omics analysis

Currently, the role of liquid-liquid phase separation (LLPS) in cancer has been preliminarily explained. However, the significance of LLPS in breast cancer is unclear. In this study, single cell sequencing datasets GSE188600 and GSE198745 for breast cancer were downloaded from the GEO database. Transcriptome sequencing data for breast cancer were downloaded from UCSC database. We divided breast cancer cells into high-LLPS group and low-LLPS group by down dimension clustering analysis of single-cell sequencing data set, and obtained differentially expressed genes between the two groups. Subsequently, weighted co-expression network analysis (WGCNA) was performed on transcriptome sequencing data, and the module genes most associated with LLPS were obtained. COX regression and Lasso regression were performed and the prognostic model was constructed. Subsequently, survival analysis, principal component analysis, clinical correlation analysis, and nomogram construction were used to evaluate the significance of the prognostic model. Finally, cell experiments were used to verify the function of the model’s key gene, PGAM1. We constructed a LLPS-related prognosis model consisting of nine genes: POLR3GL, PLAT, NDRG1, HMGB3, HSPH1, PSMD7, PDCD2, NONO and PGAM1. By calculating LLPS-related risk scores, breast cancer patients could be divided into high-risk and low-risk groups, with the high-risk group having a significantly worse prognosis. Cell experiments showed that the activity, proliferation, invasion and healing ability of breast cancer cell lines were significantly decreased after knockdown of the key gene PGAM1 in the model. Our study provides a new idea for prognostic stratification of breast cancer and provides a novel marker: PGAM1.