@ARTICLE{10.3389/fonc.2021.643065, AUTHOR={Petitprez, Florent and Ayadi, Mira and de Reyniès, Aurélien and Fridman, Wolf H. and Sautès-Fridman, Catherine and Job, Sylvie}, TITLE={Review of Prognostic Expression Markers for Clear Cell Renal Cell Carcinoma}, JOURNAL={Frontiers in Oncology}, VOLUME={11}, YEAR={2021}, URL={https://www.frontiersin.org/articles/10.3389/fonc.2021.643065}, DOI={10.3389/fonc.2021.643065}, ISSN={2234-943X}, ABSTRACT={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.} }