Dataset Information

Proteome of renal cell line caki-2 with AFMID overexpression and potential biomarker discovery in urine

ABSTRACT: Aromatic caninurine formamase (AFMID) is an enzyme involved in tryptophan pathway, metabolizing N-formylkynurenine to kynurenine. AFMID had been found significantly down regulated in clear cell renal cell carcinoma (ccRCC) in both tissue and urine samples. Although ccRCC is characterized by a typical Warburg-like phenotype, mitochondrial dysfunction and elevated fat deposition, it is unknown whether AFMID plays a role in tumorigenesis and the development of ccRCC. In present study, AFMID overexpression had inhibitory effects for ccRCC cells, decreasing the rate of cell proliferation. Quantitative proteomics showed that AFMID overexpression altered cellular signaling pathways involved in cell growth, and cellular metabolism pathways, including lipid metabolism and inositol phosphate metabolism. Further urine proteomic analysis indicated that cellular function dysfunction with AFMID overexpression could be reflected in urine. The activity of predicted up-regulators, DDX58, TREX1, TGFB1, SMARCA4, and TNF in ccRCC cells and urine showed opposing change trends. Potential urinary biomarkers were tentatively discovered and further validated using an independent cohort. Protein panel of APOC3, UMOD and LEAP2 achieved an AUC value of 0.862 for the training cohort, and 0.883 for validation cohort. Present study is of significance in terms of highlighting various aspects of pathway changes associated with AFMID enzymes, discovering potential specific biomarkers for potential patient diagnosis and therapeutic targeting.

ORGANISM(S): Homo Sapiens

SUBMITTER: Wei Sun

PROVIDER: PXD054327 | iProX | Sun Jul 28 00:00:00 BST 2024

REPOSITORIES: iProX

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Publications

Proteomics Analysis of Renal Cell Line Caki-2 with AFMID Overexpression and Potential Biomarker Discovery in Urine.

Sun Jiameng J Chang Jinchun J Guo Zhengguang Z Sun Haidan H Xu Jiyu J Liu Xiaoyan X Sun Wei W

Journal of proteome research 20240830 10

Aromatic caninurine formamase (AFMID) is an enzyme involved in the tryptophan pathway, metabolizing N-formylkynurenine to kynurenine. AFMID had been found significantly downregulated in clear cell renal cell carcinoma (ccRCC) in both tissue and urine samples. Although ccRCC is characterized by a typical Warburg-like phenotype, mitochondrial dysfunction, and elevated fat deposition, it is unknown whether AFMID plays a role in tumorigenesis and the development of ccRCC. In the present study, AFMID ...[more]

PMID: 39213636

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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.

Dataset Information

Proteome of renal cell line caki-2 with AFMID overexpression and potential biomarker discovery in urine

Publications

Proteomics Analysis of Renal Cell Line Caki-2 with AFMID Overexpression and Potential Biomarker Discovery in Urine.

Similar Datasets

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