Molecular subtyping of renal clear cell carcinoma based on prognostic RASSF family genes and validation of C1QL1 as a key prognostic marker.

RASSF family proteins play crucial roles in mitosis, apoptosis, cell migration, adhesion, and immune functions, primarily acting as tumor suppressors. Their roles in renal clear cell carcinoma (ccRCC) are not fully understood. We analyzed the expression and prognostic significance of RASSF genes in 573 ccRCC samples from TCGA and GEO, identifying two molecular subtypes with distinct characteristics. We developed a RAS score to assess prognosis and molecular status and investigated the key gene C1QL1 through in vitro assays. Four RASSF genes were identified as associated with prognosis and progression in ccRCC. Based on their co-expression, we defined two patient subtypes, one with poorer prognosis. A higher RAS score correlated with advanced disease and worse outcomes but indicated a favorable response to specific inhibitors, supporting personalized treatment strategies. Additionally, VHL mutations may cause abnormal SFMBT1 expression, leading to high C1QL1 levels, which promote tumor progression via the YAP-EMT pathway. Our findings highlight the potential of RASSF-based molecular subtypes and scoring systems in personalizing ccRCC treatment. Understanding C1QL1's role may facilitate the development of novel therapeutic approaches.