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Context:  The number of prognostic markers for clear cell renal cell carcinoma (ccRCC) has been increasing regularly over the last 15 years, without being integrated and compared.   Objective:  Our goal was to perform a review of prognostic markers for ccRCC to lay the ground for their use in the clinics.   Evidence Acquisition:  PubMed database was searched to identify RNA and protein markers whose expression level was reported as associated with survival of ccRCC patients. Relevant studies were selected through cross-reading by two readers.   Evidence Synthesis:  We selected 249 studies reporting an association with prognostic of either single markers or multiple-marker models. Altogether, these studies were based on a total of 341 distinct markers and 13 multiple-marker models. Twenty percent of these markers were involved in four biological pathways altered in ccRCC: cell cycle, angiogenesis, hypoxia, and immune response. The main genes ( VHL, PBRM1, BAP1 , and  SETD2 ) involved in ccRCC carcinogenesis are not the most relevant for assessing survival.   Conclusion:  Among single markers, the most validated markers were  KI67, BIRC5, TP53, CXCR4 , and  CA9 . Of the multiple-marker models, the most famous model, ClearCode34, has been highly validated on several independent datasets, but its clinical utility has not yet been investigated.   Patient Summary:  Over the years, the prognosis studies have evolved from single markers to multiple-marker models. Our review highlights the highly validated prognostic markers and multiple-marker models and discusses their clinical utility for better therapeutic care.

Review of Prognostic Expression Markers for Clear Cell Renal Cell Carcinoma