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Posttranslational Modifications Pattern in Clear Cell Renal Cell Carcinoma.

Corina Daniela Ene1,2, Mircea Nicolae Penescu1,2, Simona Roxana Georgescu1,3

  • 1Faculty of General Medicine, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania.

Metabolites
|December 30, 2020
PubMed
Summary

Posttranslational modifications (PTMs) like glycosylation and methylation are altered in early clear cell renal cell carcinoma (ccRCC). These PTMs offer potential biomarkers for early ccRCC diagnosis and therapeutic targets.

Keywords:
carbonylationcytokinesglycosylationmethylationnitrosative stressphosphorylationposttranslational modificationprotein cleavagerenal cell carcinomathiol/disulfide equilibrium

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Area of Science:

  • Biochemistry
  • Oncology
  • Molecular Biology

Background:

  • Posttranslational modifications (PTMs) are crucial enzymatic processes implicated in cancer development.
  • Understanding PTMs in clear cell renal cell carcinoma (ccRCC) pathogenesis is vital for early detection and treatment.

Purpose of the Study:

  • To investigate the significance of various PTMs in the pathogenesis of localized ccRCC.
  • To identify potential serum biomarkers for early ccRCC diagnosis.

Main Methods:

  • A prospective, observational study over three years.
  • Inclusion of 55 patients with localized ccRCC and 30 healthy controls.
  • Evaluation of glycosylation, nitration, carbonylation, thiol-disulfide homeostasis, methylation, phosphorylation, and proteolytic cleavage in serum.

Main Results:

  • Early ccRCC exhibits high cytokine production, substrate hypersialylation, and nitrosative/carbonylic stress.
  • Alterations in arginine methylation and thiol-disulfide homeostasis (TDH) were observed.
  • Soluble receptors (sRAGE, sIL-6R) regulate RAGE/IL-6 signaling, with TK-1 and TuM2-PK modulating phosphometabolites.

Conclusions:

  • Identified PTMs and metabolites (e.g., sialic acid, nitrotyrosine, ADMA, SDMA, TDH) may serve as early diagnostic biomarkers for ccRCC.
  • PTM signatures could indicate disease progression and represent therapeutic targets in kidney oncogenesis.