AUTHOR=Petitprez Florent , Ayadi Mira , de Reyniès Aurélien , Fridman Wolf H. , Sautès-Fridman Catherine , 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/journals/oncology/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.