Comprehensive Analysis of the Expression, Prognosis, and Biological Significance of PLOD Family in Bladder Cancer

Abstract

Background

Large numbers of studies have identified that procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family members play important roles in tumorigenesis and tumor progression in various cancers. However, the expression pattern, clinical value and function of PLOD family have yet to be analyzed systematically and comprehensively in bladder urothelial carcinoma (BLCA).

Methods

We investigated the transcriptional levels, genetic alteration, biological function, immune cell infiltration, data on survival of PLODs in patients with BLCA based on UALCAN, the Cancer Genome Atlas (TCGA) database, Gene Expression Profiling Interactive Analysis (GEPIA), TIMER, STRING, cBioPortal and GSCALite databases. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed in R software using the Cluster Profiler Bioconductor package. Protein–protein interaction (PPI) network was established by STRING and visualized by using R version (3.6.3) software. Survival analysis was performed using the packages “survminer”.

Results

The mRNA and protein expression patterns of PLOD family members were noticeably increased in BLC compared with normal tissue. The mRNA expression levels of PLOD1-2 genes were significantly correlated with histological subtypes and PLOD1 was significantly correlated with pathological stage. Furthermore, the high expression levels of PLOD1-2 were remarkably associated with poor overall survival (OS) in BLCA patients, meanwhile high expression levels of PLOD1 and PLOD3 were markedly associated with poor progression-free interval (PFI). In co-expression gene analysis, 50 genes were primarily associated with the differentially expressed PLODs in BLCA. Functional enrichment analysis revealed that protein hydroxylation, collagen fibril organization, and lysine degradation were key biological functions of PLODs in BLCA. Moreover, PLOD family genes were identified as being associated with the activities of tumor-infiltrating immune cells and closely associated with immune responses in BLCA.

Conclusion

PLOD family members might serve as potential therapeutic targets and prognostic markers for BLCA patients’ survival.

Keywords:

• bladder cancer
• PLODs
• immune infiltration
• prognosis
• biomarker

Data Sharing Statement

All relevant data are within the manuscript.

Ethics Approval and Consent to Participate

According to the Declaration of Helsinki’s ethical principles, the study was conducted. The fresh bladder cancer tissues and adjacent normal tissues were collected from the First Affiliated Hospital of Nanchang University, which was approved by the Human Research Ethics Committee of this hospital. The written informed consent was collected from each patient.

Acknowledgments

The authors would like to thank the patients who participated in this study, and two independent senior pathologists for technical support. Ru Chen and Ming Jiang are co-first authors for this study.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

This work was supported by Grant 2021QNA070 for Youth Research Fund from Fujian Provincial Health Commission, China.