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

Gęgotek, Agnieszka; Brańska-Januszewska, Justyna; Samocik, Paweł; Kozłowski, Robert; Koda, Mariusz; Žarković, Neven; Skrzydlewska, Elżbieta; Ostrowska, Halina (2025) Protein modifications by advanced glycation end products (AGEs) in human clear cell renal cell carcinoma. Journal of Translational Medicine, 23 (1). ISSN 1479-5876

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Abstract

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). A proteomic approach (SDS-PAGE/HPLC/MS–MS) with partial validation based on 2D-SDS-PAGE-Western blot was used to identify protein modifications by AGEs in cancer tissue samples of 16 patients with ccRCC compared to respective non-tumor kidney tissues of the same patients. The findings revealed elevated levels of carboxymethylation/carboxyethylation along with the increased formation of pyrraline, argpyrimidine, and pentosidine on cysteine, lysine, or arginine residues in tumor tissues compared to matched non-tumor kidney tissue. Albumin was identified as a target for AGE modifications in its pre-proalbumin and mature forms. Most of the AGE-modified proteins in ccRCC tissues were involved in catalytic and binding functions, regulation, transcription and transport. These proteins were distributed throughout the cell, including the nucleus, as confirmed by immunofluorescence analysis. Of note, five of ten AGE-modified glycolytic enzymes were found exclusively in ccRCC tissues. This study demonstrates a distinct AGE-modified proteome in ccRCC compared to non-tumor tissue, with modifications frequently occurring within or near functional domainst. Therefore, further investigation into the mechanisms underlying AGE-protein adduct formation in renal carcinogenesis could help in understanding ccRCC development.

Item Type:	Article
Uncontrolled Keywords:	Advanced glycation end products (AGEs); Protein modification; Proteomics; Kidney disease; Tumor; Clear cell renal cell carcinoma (ccRCC)
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions:	Division of Molecular Medicine
Depositing User:	Ema Buhin Šaler
Date Deposited:	09 Jan 2026 15:04
URI:	http://fulir.irb.hr/id/eprint/10782
DOI:	10.1186/s12967-025-06958-6

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