Abstract: 【Abstract】 Objective To analyze the serum proteomic profiles and their diagnostic value in male patients with male pattern hair loss （MPHL）. Methods （1） Discovery population: serum samples from MPHL patients （MPHL group） and age- and sex-matched （1∶1） non-MPHL controls （control group） were selected based on accession order and systematic sampling from the Dermatological Epidemiological Survey Project at the Shenzhen Center for Chronic Disease Control between June 2023 and September 2024. The data-independent acquisition label-free quantitative （DIA-LFQ） proteomics technology combined with R software was used to screen differentially expressed proteins （DEPs） between the two groups, and Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed. （2） Validation population: another set of serum samples from MPHL patients （MPHL group） and age- and sex-matched （1∶1） non-MPHL controls （control group） was selected from the aforementioned epidemiological survey project. The screened DEPs were validated using enzyme-linked immunosorbent assay （ELISA）. Statistical analysis was carried out by using the two independent samples t-test and Mann-Whitney U test for comparisons between groups. Spearman correlation analysis was conducted to evaluate correlations between DEPs and biochemical parameters. The diagnostic performance of DEPs for MPHL was evaluated using receiver operating characteristic （ROC） curves and areas under the curve （AUCs）. Results （1） Discovery population: 33 MPHL patients were included in the MPHL group and 33 non-MPHL controls in the control group. A total of 34 DEPs were identified via the DIA-LFQ technology. Compared with the control group, 18 proteins were downregulated and 16 were upregulated in the MPHL group （all P < 0.05）. GO analysis revealed that these DEPs were primarily enriched in biological processes such as membrane ruffling and regulation of actin filament-related processes, cellular components such as the specific granule lumen, and molecular functions including scavenger receptor activity and glycosaminoglycan binding. KEGG analysis indicated that these DEPs were mainly involved in pathways such as leukocyte transendothelial migration. ROC curve analysis showed that 6 DEPs had potential diagnostic value for MPHL （AUCs: 0.65 - 0.67, all P < 0.05）, including calponin 2, proteoglycan 4, transthyretin, pleckstrin, protein Z-dependent protease inhibitor, and hepatic lipase （LIPC）. （2） Validation population: 83 MPHL patients were included in the MPHL group and 83 non-MPHL controls in the control group. ELISA showed that the expression level of LIPC was significantly higher in the MPHL group （median ［Q1, Q3］: 2.98 ［2.65, 3.56］ ng/ml） than in the control group （2.80 ［2.53, 3.29］ ng/ml, Z = -2.14, P = 0.032）. Spearman correlation analysis revealed positive correlations of LIPC levels with the homeostasis model assessment of insulin resistance （HOMA-IR） index and insulin levels （both rs = 0.24, both P < 0.05） in the MPHL group. ROC curve analysis demonstrated that LIPC had potential diagnostic value for MPHL, with an AUC （95% CI） of 0.60 （0.52, 0.69） （P = 0.021）, a sensitivity of 0.58, and a specificity of 0.63. Conclusion Based on the DIA-LFQ technology, the upregulation of LIPC in the serum of MPHL patients was identified and validated, suggesting that LIPC may serve as a novel candidate biomarker for the early diagnosis of MPHL.

Key words: Alopecia, Male androgenetic alopecia, DIA-LFQ proteomics technology, Hepatic lipase