Serum proteomic profiling reveals LPA As a biomarker for paraspinal muscle fat infiltration in degenerative lumbar kyphosis

Abstract

Paraspinal muscle fat infiltration (PMFI) plays a crucial role in the onset and progression of degenerative lumbar kyphosis (DLK). Dynamic identification and validation of serum potential biomarkers could facilitate assessment of PMFI status. A total of 47 patients with DLK and 44 patients with lumbar spinal stenosis (LSS) were included in the study. The relative cross-sectional area (rCSA) and the fat infiltration rate (FI%) of paraspinal muscle were measured at the L2-3 level. Serum samples were collected for proteomic profiling. Candidate protein was validated in an independent cohort. Oil Red O staining was applied to assess PMFI. Immunofluorescence staining was performed to quantify the expression level of candidate protein. Pearson correlation analysis and Receiver Operating Characteristic (ROC) curve were used to evaluate the associations between candidate biomarker expression level and PMFI, as well as the sagittal vertical axis (SVA). DLK patients exhibit a significantly higher PMFI than LSS. Through Data-Independent Acquisition (DIA) proteomic profiling, we identified 216 differentially expressed proteins (DEPs) (|Fold Change cutoff|> 1.5, P <0.05), among which 19 proteins were upregulated and 197 proteins were downregulated. Gene Ontology (GO) analysis revealed significant enrichment of biological processes related to lipid metabolism and energy metabolism. The serum lipoprotein(a) (LPA) was identified as a potential candidate among the upregulated proteins. Immunofluorescent staining of paraspinal muscle suggested LPA expression was higher in DLK patients. Moreover, correlation analyses indicated serum LPA levels were positively associated with PMFI (R=0.68, P<0.05) and sagittal imbalance (R=0.61, P<0.05) in patients with DLK. ROC curve revealed that serum LPA is an important predictive factor for PMFI (Area Under the Curve (AUC)=0.79) and sagittal imbalance (AUC=0.74) in DLK patients. This study profiles the serum proteomics of patients with DLK, highlighting LPA as a putative biomarker that reflects PMFI and sagittal imbalance.