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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Microbial Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1639997

This article is part of the Research TopicDeciphering Host-Pathogen Interactions in Tuberculosis: Implications for Diagnostics and TherapeuticsView all 11 articles

Diagnostic Potential of WNT Signaling Gene Methylation in Pulmonary Tuberculosis

Provisionally accepted
Hua  WangHua Wang1Chao-Cai  WangChao-Cai Wang2Qian  HuangQian Huang3Yu  XiaoYu Xiao1Yin  HanYin Han1Lei  XieLei Xie1Yan  LiuYan Liu4*Yan-Jun  XiongYan-Jun Xiong1
  • 1Anhui Chest Hospital, Hefei, China
  • 2Qing Hai Center for Disease Prevention and Control, Xining, China
  • 3Anhui Medical University, Hefei, China
  • 4Qinghai University, Xining, China

The final, formatted version of the article will be published soon.

Objectives: The WNT signaling pathway plays important roles in the pathophysiology of pulmonary tuberculosis (PTB). This study aimed to assess the association of the DNA methylation levels of WNT signaling pathway genes and PTB susceptibility, and determine whether the methylation levels might serve as valuable biomarkers for PTB diagnosis. Methods: We collected blood samples from 98 PTB patients and 96 normal controls, and extracted DNA samples. The methylation levels of promoter region in WNT signaling pathway genes (SFRP1, WNT3A, CTNNB1, WIF-1, DKK-1, LRP5, LRP6) were detected by MethylTarget technique. Results: We found that the methylation levels of SFRP1, WNT3A, CTNNB1, DKK-1, LRP6 genes were significantly decreased in the peripheral blood of PTB patients when compared to normal controls, while WIF-1, LRP5 genes methylation levels showed no significant difference between PTB patients and controls. In PTB patients, the increased SFRP1 methylation level was significantly correlated with drug-induced liver injury, pulmonary infection, and the decreased WNT3A, CTNNB1 methylation levels were respectively significantly associated with drug resistance, fever. For diagnosing PTB, the CTNNB1 methylation level demonstrated a relatively higher diagnostic value, achieving an AUC of 0.706. Subsequently, the AUC of WNT3A, DKK-1, LRP6 was 0.660, 0.628, 0.621. The diagnostic value was slightly enhanced when CTNNB1 combined with WNT3A, DKK-1, LRP6, with an AUC of 0.710. Conclusion: The methylation levels of SFRP1, WNT3A, CTNNB1, DKK-1, LRP6 genes were significantly decreased in PTB patients, and single gene or multiple genes emerge 删除[COM]: methylation panels might serve as potential diagnostic biomarkers for PTB.

Keywords: pulmonary tuberculosis, DNA Methylation, WNT signaling pathway genes, Tuberculosis, epigenetics

Received: 03 Jun 2025; Accepted: 20 Oct 2025.

Copyright: © 2025 Wang, Wang, Huang, Xiao, Han, Xie, Liu and Xiong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yan Liu, yanliu@qhu.edu.cn

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