Molecular Components of the RCC Grade

Semin Nephrol. 2020 Jan;40(1):14-27. doi: 10.1016/j.semnephrol.2019.12.003.


Clear cell renal cell carcinoma (ccRCC) is a major cancer yet has long evaded extensive efforts to target it chemotherapeutically. Recent efforts to characterize its proteome and metabolome in a grade-defined manner has resulted in a global proteometabolomic reprogramming model yielding a number of potential drug targets, many of which are under the control of transcription factor and MYC proto-oncogene, bHLH transcription factor. Furthermore, through the use of conventional technologies such as immunohistochemistry, protein moonlighting, a phenomenon wherein a single protein performs more than one distinct biochemical or biophysical functions, is emerging as a second mode of operation for ccRCC metabolo-proteomic reprogramming. This renders the subcellular localization of the grade-defining biomarkers an additional layer of grade-defining ccRCC molecular signature, although its functional significance in ccRCC etiology is only beginning to emerge.

Keywords: Fuhrman nuclear grade-defining biomarkers; Myc; metabolo-proteomics; protein moonlighting.

Publication types

  • Review

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology*
  • Cellular Reprogramming
  • Citric Acid Cycle
  • Gluconeogenesis
  • Glutathione / metabolism
  • Glycolysis
  • Humans
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology*
  • Metabolomics
  • Neoplasm Grading
  • Proteomics
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc
  • Urea / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc
  • Urea
  • Glutathione