Dataset Information

Protein modifications by advanced glycation end products (AGEs) in human clear cell renal cell carcinoma

ABSTRACT: The development of clear cell renal cell carcinoma (ccRCC) is connected with disturbed glycolytic processes leading to the highly reactive dicarbonyls generation, resulting in protein modifications by advanced glycation end products (AGEs). Therefore, the present study aimed to analyze the level of major AGE-protein adducts and identify modified proteins using a proteomic approach in ccRCC tissue of cancer patients compared to nonchanged tissue. The obtained results indicated a higher level of carboxymethylation/carboxyethylation and increased formation of pyrraline, argpyrimidine and pentosidine on cysteine, lysine or arginine residues in tumor tissue comparing to non-tumor kidney tissue. The main protein creating adducts with AGEs was albumin in both forms, pre-proalbumin and mature protein. The majority of the AGE-modified proteins in ccRCC tissues were proteins with catalytic and binding activity, regulators, transporters, and transcription activity, localized in cellular components, including nucleus what was confirmed by immunofluorescence assay. Within ten glycolytic enzymes modified by AGEs, five were indicated only in ccRCC tissue. Summarizing, obtained results clearly indicates the role of AGEs and their adducts formation with proteins in the development of kidney tumor. Moreover, it can be concluded that there is a real possibility of using knowledge regarding the consequences of the formation of AGE-protein connections in the assessment of the therapy effectiveness.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Kidney

SUBMITTER: Agnieszka Gęgotek

LAB HEAD: Agnieszka Gęgotek

PROVIDER: PXD059009 | Pride | 2026-02-09

REPOSITORIES: Pride

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Publications

Protein modifications by advanced glycation end products (AGEs) in human clear cell renal cell carcinoma.

Gęgotek Agnieszka A Brańska-Januszewska Justyna J Samocik Paweł P Kozłowski Robert R Koda Mariusz M Zarkovic Neven N Skrzydlewska Elżbieta E Ostrowska Halina H

Journal of translational medicine 20250814 1

<h4>Background</h4>The development of cancer is often associated with altered glycolytic processes, resulting in the accumulation of highly reactive dicarbonyl compounds that promote protein modifications through advanced glycation end products (AGEs). This study aimed to quantify and identify the major AGE-modified proteins in clear cell renal cell carcinoma (ccRCC).<h4>Methods</h4>A proteomic approach (SDS-PAGE/HPLC/MS-MS) with partial validation based on 2D-SDS-PAGE-Western blot was used to i ...[more]

PMID: 40813989

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Project description:Patients with loss-of-function mutations of the von Hippel Lindau gene (“VHL-patients”) often develop clear cell renal cell carcinoma (ccRCC). Using archived, formalin-fixed, paraffin-embedded (FFPE) samples and a cohort of eight cases, we sought to determine global proteome alterations that distinguish ccRCC tissue from adjacent, non-malignant kidney tissue in VHL-patients. Our quantitative proteomic analysis clearly discriminated tumor and non-malignant tissue, yielding comparable proteome profiles for the eight ccRCC cases. Limma statistics was used to identify significantly dysregulated proteins in ccRCC. Functional classification of these proteins highlighted a decrease in proteins involved in the tricarboxylic acid cycle and an increase in proteins involved in glycolysis. This profile possibly represents a proteomic fingerprint of the “Warburg effect”, which is a molecular hallmark of ccRCC. Furthermore, we observed an increase in proteins involved in extracellular matrix organization. Of particular note were opposing alterations of Xaa-Pro Aminopeptidases-1 and -2 (XPNPEP-1 and -2): a strong decrease of XPNPEP-2 in ccRCC was accompanied by a strong increase of the related protease XPNPEP-1. In both cases, we corroborated the proteomic results by immunohistochemical analysis of ccRCC and adjacent, non-malignant kidney tissue of VHL patients. To functionally investigate the role of XPNPEP-1 in ccRCC, we performed small-hairpin RNA mediated XPNPEP-1 expression silencing in 786-O ccRCC cells harboring a mutated VHL gene. We found that XPNPEP-1 expression suppresses cellular proliferation and migration. These results suggest that XPNPEP-1 is rather an anti-target in VHL-driven ccRCC. Generally, we present one of the first proteomic profiling studies of ccRCC in VHL patients, comparing normal and tumor tissue, which are both deficient for the VHL tumor suppressor. Methodologically, our work further validates the robustness of using FFPE material for quantitative proteomics.

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Dataset Information

Protein modifications by advanced glycation end products (AGEs) in human clear cell renal cell carcinoma

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Publications

Protein modifications by advanced glycation end products (AGEs) in human clear cell renal cell carcinoma.

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