Prognostic Significance of Elevated UCHL1, SNRNP200, and PAK4 Expression in High-Grade Clear Cell Renal Cell Carcinoma - LC-MS/MS and Immunohistochemical Validation

Sep 21, 2026

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Recent proteomics advances improve understanding of clear cell renal cell carcinoma (CCRCC). This study used liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by immunohistochemical validation to quantify UCHL1, PAK4, and SNRNP200 in high-grade CCRCC. Reactome pathway enrichment was integrated to define cancer-related functions. Results showed significant UCHL1 and SNRNP200 upregulation and PAK4 downregulation in tumor versus non-cancer tissues. UCHL1 linked to Akt signaling, SNRNP200 to RNA splicing and cell-cycle progression, and PAK4 to proliferation and invasion. Expression patterns associated with poorer progression-free survival, supporting their prognostic value and potential therapeutic targets in aggressive CCRCC.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

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Introduction

Disease background and incidence

Genetics and risk factors

Clinical diagnosis and imaging

cancers Article Prognostic Significance of Elevated UCHL1, SNRNP200, and PAK4 Expression in High-Grade Clear Cell Renal Cell Carcinoma: Insights from LC-MS/MS Analysis and Immunohistochemical Validation Michał Kasperczak 1, *, Gabriel Bromi ´nski 1, Iga Kołodziejczak-Guglas 2, Andrzej Antczak 1 and Maciej Wiznerowicz 1,2,3 1 Department of Urology, Pozna ´n University of Medical Sciences, 61-701 Pozna ´n, Poland 2 International Institute for Molecular Oncology, 60-203 Pozna ´n, Poland 3 University Hospital of Lord’s Transfiguration, 61-848 Pozna ´n, Poland * [Correspondence: mkasperczakmd@gmail.com](Correspondence: mkasperczakmd@gmail.com); Tel.: +48-693964628 Citation: Kasperczak, M.; Bromi ´nski, G.; Kołodziejczak-Guglas, I.; Antczak, A.; Wiznerowicz, M. Prognostic Significance of Elevated UCHL1, SNRNP200, and PAK4 Expression in High-Grade Clear Cell Renal Cell Carcinoma: Insights from LC-MS/MS Analysis and Immunohistochemical Validation. Cancers 2024, 16, 2844 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers16162844 Academic Editor: Evgeny Yakirevich Received: 10 July 2024 Revised: 7 August 2024 Accepted: 10 August 2024 Published: 14 August 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . Simple Summary: This study explored the protein expression levels of UCHL1, SNRNP200, and PAK4 in clear cell renal cell carcinoma (CCRCC) using advanced proteomic techniques. We found that UCHL1 and SNRNP200 are significantly upregulated, and PAK4 is downregulated in high-grade CCRCC, and all are involved in critical cellular pathways linked to cancer progression and poor clinical outcomes. Specifically, UCHL1 is implicated in the Akt signaling pathway, SNRNP200 plays a role in RNA splicing and cell cycle regulation, and PAK4 is associated with cell proliferation and invasion. The enhanced expression of UCHL1 and SNRNP200, and decreased expression of PAK4 correlate with shorter progression-free survival in CCRCC patients, suggesting their potential as prognostic markers and targets for therapeutic intervention. This research contributes to the understanding of CCRCC’s molecular dynamics and opens new avenues for targeted treatments. Abstract: Recent advancements in proteomics have enhanced our understanding of clear cell renal cell carcinoma (CCRCC). Utilizing a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by immunohistochemical validation, we investigated the expression levels of UCHL1, PAK4, and SNRNP200 in high-grade CCRCC samples. Our analysis also integrated Reactome pathway enrichment to elucidate the roles of these proteins in cancer-related pathways. Our results revealed significant upregulation of UCHL1 and SNRNP200 and downregulation of PAK4 in high-grade CCRCC tissues compared to non-cancerous tissues. UCHL1, a member of the ubiquitin carboxy-terminal hydrolase family, showed variable expression across different tissues and was notably involved in the Akt signaling pathway, which plays a critical role in cellular survival in various cancers. SNRNP200, a key component of the RNA splicing machinery, was found to be essential for proper cell cycle progression and possibly linked to autosomal dominant retinitis pigmentosa. PAK4’s role was noted as critical in RCC cell proliferation and invasion and its expression correlated significantly with poor progression-free survival in CCRCC. Additionally, the expression patterns of these proteins suggested potential as prognostic markers for aggressive disease phenotypes. This study confirms the upregulation of UCHL1, SNRNP200, and PAK4 as significant factors in the progress

FAQs

What methodology was used to measure UCHL1, SNRNP200, and PAK4 in this study?

The study quantified protein expression using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and confirmed findings with immunohistochemical validation.

How do UCHL1, SNRNP200, and PAK4 expression levels differ between high-grade CCRCC and non-cancer tissues?

UCHL1 and SNRNP200 were significantly upregulated, while PAK4 was downregulated in high-grade CCRCC tissues compared with non-cancer tissues.

Why might these proteins be clinically important in CCRCC?

Their expression patterns correlated with shorter progression-free survival, suggesting UCHL1, SNRNP200, and PAK4 as potential prognostic markers and therapeutic targets.

Sep 21, 2026

Uploaded by Asher