The hMeDIP-Seq Identified INPP4A as a Novel Biomarker for Eosinophilic Chronic Rhinosinusitis with Nasal Polyps

Abstract

Background: Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is an endotype of chronic rhinosinusitis with nasal polyps characterized by more severe symptoms, a stronger association with asthma and a greater recurrence risk. It is unknown whether DNA hydroxymethylation could influence ECRSwNP. Methods: Hydroxymethylated DNA immunoprecipitation sequencing was carried out in three distinct groups (control, ECRSwNP and NECRSwNP). Additional qRT-PCR, immunohistochemistry and analysis of the receiver operating characteristic curve were performed. Results: Between ECRSwNP and NECRSwNP, 26 genes exhibited differential DNA hydroxymethylation. Consistent with their hydroxymethylation level, GNAL, INPP4A and IRF4 expression levels were significantly different between ECRSwNP and the other two groups. The receiver operating characteristic curve revealed that INPP4A mRNA has a high predictive accuracy for ECRSwNP. Conclusion: DNA hydroxymethylation regulates the expression of multiple genes in ECRSwNP. INPP4A mRNA was markedly decreased in ECRSwNP polyps and can predict ECRSwNP.

Keywords::

• biomarker
• DNA hydroxymethylation
• eosinophilic chronic rhinosinusitis with nasal polyps
• GNAL
• INPP4A
• IRF4
• predictive value

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2022-0053

Author contributions

H Tan, X Tong and Z Gao contributed equally to the study. H Tan and X Tong performed the research and analyzed the data. H Tan, X Tong and Z Gao wrote the manuscript. Y Xu and L Tan provided samples and experimental advice. W Zhang and R Xiang made substantial contributions to the conception and design of the study. Y Xu supervised the study. All authors read and approved the final manuscript.

Financial&competing interests disclosure

This research was supported by the National Natural Science Foundation of China (no. 82071017), the National Natural Science Foundation of Hubei Province (no. 2021CFB125) and the Fundamental Research Funds for the Central Universities (nos. 2042020kf1044 and 2042021kf0093). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that was approved by Ethics Committee of Renmin Hospital of Wuhan University (WDRM2021-K084). In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This research was supported by the National Natural Science Foundation of China (no. 82071017), the National Natural Science Foundation of Hubei Province (no. 2021CFB125) and the Fundamental Research Funds for the Central Universities (nos. 2042020kf1044 and 2042021kf0093). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.