Integrative analysis of bulk RNA and single-cell sequencing data reveals a liquid-liquid phase separation signature for clear cell renal cell carcinoma.

Liquid-liquid phase separation (LLPS) is a significant biophysical phenomenon that plays a crucial role in numerous pathophysiological processes associated with tumors. This study aims to establish a prognostic and immunotherapeutic response prediction signature for clear cell renal cell carcinoma (ccRCC) based on LLPS-related genes. Firstly, 66 differentially expressed LLPS-related genes were obtained from the TCGA, and then the LLPS prognostic signature constructed from five genes, including HOXA13, TEAD4, KMT5C, TRNP1, and SGO1, was identified by univariate Cox and least absolute shrinkage and selection operator algorithm. Meanwhile, the results of Kaplan-Meier analysis, ROC curves, principal component analysis, and nomogram showed high reliability of the constructed LLPS signature. Additionally, the relationship between the signature and immune infiltration, immunotherapy, and sensitivity to targeted therapeutic agents was discussed in this study. Single-cell sequencing data were used to analyze the expression levels of the signature genes in different cells in the ccRCC microenvironment. Finally, the expression of the signature genes was verified in ccRCC cells, and the effect of SGO1 on the malignant biological behavior of ccRCC cells was also verified by in vitro experiments. In conclusion, this LLPS prognostic signature may be a potential clinical prognostic and immunotherapeutic response-related indicator for ccRCC patients.