Identification of PLOD3 and LRRN3 as potential biomarkers for Parkinson's disease based on integrative analysis

Xing Guo; Wenjun Hu; Zijie Gao; Yang Fan; Qianqian Wu; Weiguo Li

doi:10.1038/s41531-023-00527-8

Identification of PLOD3 and LRRN3 as potential biomarkers for Parkinson's disease based on integrative analysis

NPJ Parkinsons Dis. 2023 May 31;9(1):82. doi: 10.1038/s41531-023-00527-8.

Authors

Xing Guo^#^{1

2}, Wenjun Hu^#³, Zijie Gao^#^{1

2}, Yang Fan^{1

2}, Qianqian Wu¹, Weiguo Li^{4

5}

Affiliations

¹ Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, 250012, Jinan, Shandong, China.
² Shandong Key Laboratory of Brain Function Remodeling, 250012, Jinan, Shandong, China.
³ Department of General Practice, Central Hospital Affiliated to Shandong First Medical university, 250000, Jinan, Shandong, China.
⁴ Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, 250012, Jinan, Shandong, China. leeweiguo_777@126.com.
⁵ Shandong Key Laboratory of Brain Function Remodeling, 250012, Jinan, Shandong, China. leeweiguo_777@126.com.

^# Contributed equally.

Abstract

Parkinson's disease (PD) is one of the most prevalent movement disorders and its diagnosis relies heavily on the typical clinical manifestations in the late stages. This study aims to screen and identify biomarkers of PD for earlier intervention. We performed a differential analysis of postmortem brain transcriptome studies. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify biomarkers related to Braak stage. We found 58 genes with significantly different expression in both PD brain tissue and blood samples. PD gene signature and risk score model consisting of nine genes were constructed using least absolute shrinkage and selection operator regression (LASSO) and logistic regression. PLOD3 and LRRN3 in gene signature were identified to serve as key genes as well as potential risk factors in PD. Gene function enrichment analysis and evaluation of immune cell infiltration revealed that PLOD3 was implicated in suppression of cellular metabolic function and inflammatory cell infiltration, whereas LRRN3 exhibited an inverse trend. The cellular subpopulation expression of the PLOD3 and LRRN3 has significant distributional variability. The expression of PLOD3 was more enriched in inflammatory cell subpopulations, such as microglia, whereas LRRN3 was more enriched in neurons and oligodendrocyte progenitor cells clusters (OPC). Additionally, the expression of PLOD3 and LRRN3 in Qilu cohort was verified to be consistent with previous results. Collectively, we screened and identified the functions of PLOD3 and LRRN3 based the integrated study. The combined detection of PLOD3 and LRRN3 expression in blood samples can improve the early detection of PD.