Comprehensive profiling of RPP40 across human cancers reveals its essential role and multidimensional clinical correlates

Ribonuclease P/MRP subunit p40 (RPP40) is a core component of the RNase P/MRP ribonucleoprotein complex, playing a central role in RNA processing. However, its systematic characteristics, clinical significance, and functional mechanisms at the pan-cancer level remain unclear. We systematically characterized the pan-cancer expression profile and prognostic value of RPP40 using multi-omics approaches, including pan-cancer expression profiling, CRISPR screening, single-cell RNA sequencing, immunohistochemistry, proteomics, and multi-level survival analyses. We further examined correlations between RPP40 expression and diverse clinical indicators, including tumor stage, treatment response, immune subtype, and demographic characteristics. RPP40 expression was significantly upregulated in most cancers and their subtypes, and it was identified as a broadly essential gene for cancer cell survival. High RPP40 expression was significantly associated with advanced tumor stage and poor prognosis, serving as an independent risk factor for overall survival and progression-free survival across multiple independent cohorts. Our multidimensional analytical framework further revealed significant associations between RPP40 expression and various features, including pathological stage, major tumor subtypes, and smoking history. Functionally, RPP40 likely promotes tumor proliferation by activating cell cycle pathways, and its expression displays strong cell cycle dependency. This study systematically elucidates the oncogenic role of RPP40 across cancers, establishing it as a novel and translationally promising pan-cancer prognostic biomarker and a potential therapeutic target. The “multi-level clinical–molecular integrative analysis” framework developed herein provides foundational evidence and data support for subsequent precision therapeutic strategies targeting RPP40.