Potential biomarkers for psoriasis topical treatment by in-depth serum proteomics

Abstract

Background

Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical treatment. However, the exact mechanism by which this treatment regimen relieves psoriasis is unknown.

Method

We assembled a cohort of 65 psoriasis patients and divided post-treatment cohort into responder group and non-responder group according to the Psoriasis Area Severity Index (PASI) score after 12-week treatment. We measured the expression levels of proteins in collected 130 serum samples using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the responder group and constructed a proteomics landscape of psoriasis pathogenesis response to treatment. We then validated the biomarkers of disease severity in an independent cohort of 88 samples using an enzyme-linked immunosorbent assay.

Results

We first identified 174 differentially expressed proteins (DEPs) for comparative analysis of proteins between responders and non-responders at baseline (p < 0.05). Then pathway analysis showed that the responders focused more on signaling molecules and interaction, complement and coagulation cascades, whereas the non-responders more on signal transduction and IL-17 signaling pathways. We further identified four candidate biomarkers (COLEC11, C1QA, BNC2, ITIH4) response to treatment. We also found 125 DEPs (p < 0.05) after treatment compared with before treatment in responder group. Pathway analysis showed an enrichment in pathways related to complement and coagulation cascades, phagosome, ECM-receptor interaction, cholesterol metabolism, vitamin digestion and absorption. CD14 was validated as potential biomarkers for the disease severity of psoriasis and treatment targets.

Conclusion

In this work, we analyzed the response to topical sequential therapy and finally identified four biomarkers. Additionally, we found that topical sequential therapy may alleviate psoriasis by regulating lipid metabolism and modulating the immune response by affecting the complement activation process.

Keywords:

• Calcipotriol
• calcipotriol betamethasone
• psoriasis
• serum proteomics
• biomarker
• antibody microarray;DIA-MS

Author contributions

J. C. and X. Z. executed the array experiments, sample preparation and DIA-MS experiments; J. D., Y. Y., D. Y., H. D., J. Y. and S. Y. collected the serum samples and clinical information; J. C., and X. Z. executed the data analysis; C. L., L. H. and X. Y. designed and supervised all experiments and wrote the paper. All authors approved the final manuscript.

Disclosure statement

The authors declare that they have no competing interests.

Data availability statement

The data that supporting the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Additional information

Funding

This project was financially supported by the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macau Joint Lab), No: 2020B1212030006;2022 TCM Innovation Team and Talent Support Program of the State Administration of Traditional Chinese Medicine, No: ZYYCXTD-C-202204; State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, No:SZ2021ZZ45; National Key Technology R&D Program for the 12th Five-year Plan of Ministry of Science and Technology, No:2013BAI02B03; the Program on the Joint Proteomics Center for Chinese Medicine between PHOENIX Center and Guangdong Provincial Academy of Chinese Medical Sciences, No:YN2021DB03.