# Prognostic biomarker and clinical significance of PLOD gene family in clear cell renal cell carcinoma

## TL;DR

This study explores the role of the PLOD gene family in kidney cancer, finding that high PLOD levels are linked to worse outcomes and identifying acetaminophen as a potential treatment target.

## Contribution

The study identifies PLOD genes as prognostic biomarkers in ccRCC and suggests acetaminophen as a potential modulator of PLOD activity.

## Key findings

- PLOD1, PLOD2, and PLOD3 are overexpressed in ccRCC tissues and cell lines.
- High PLOD expression correlates with reduced survival and therapy resistance in ccRCC.
- Acetaminophen is identified as a potential regulator of all three PLOD proteins.

## Abstract

The PLOD gene family, involved in extracellular matrix (ECM) remodeling, plays a role in tumor progression, but its comprehensive role and clinical significance in clear cell renal cell carcinoma (ccRCC) remains unclear.

We integrated multi-omics bioinformatics analyses from public databases (TCGA, GEO) with experimental validation using RT-qPCR, western blotting, and functional assays to systematically evaluate the expression patterns, prognostic value, immune microenvironment associations and drug resistance of PLOD genes in ccRCC. Computational approaches, including the comparative toxicogenomics database and molecular docking, were further employed to identify potential chemical modulators.

PLOD1, PLOD2, and PLOD3 were consistently overexpressed at both mRNA and protein levels in ccRCC tissues and cell lines. High PLOD expression was significantly correlated with reduced overall survival, and poor disease-free survival. Functional enrichment analysis revealed the involvement of PLOD gene family in collagen biosynthesis, ECM-receptor interaction, and lysine degradation pathways. PLOD expression was also linked to an immunosuppressive microenvironment and resistance to conventional therapeutics. Through toxicogenomics screening and molecular docking, acetaminophen was identified as a potential regulator of all three PLOD proteins.

This study underscores the pivotal role of the PLOD family in ccRCC pathogenesis through ECM remodeling, immune modulation, and therapy resistance. Our results support their utility as diagnostic and prognostic biomarkers, and acetaminophen may serve as a candidate for targeting PLOD-mediated pathways, providing a foundation for future preclinical and therapeutic investigations.