Skip to main content

ORIGINAL RESEARCH article

Front. Oncol.
Sec. Breast Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1408723

Investigating the Role of Cathepsins in Breast Cancer Progression: A Mendelian randomization Study

Provisionally accepted
Shengyi Zhou Shengyi Zhou 1*Yizhou Sun Yizhou Sun 2,3Wenzhang Zha Wenzhang Zha 2,3*Guangjun Zhou Guangjun Zhou 2,3*
  • 1 School of Medicine, Xiamen University, Xiamen, Fujian, China
  • 2 Yancheng First Hospital，Affiliated Hospital of Nanjing University Medical School, Yancheng, China
  • 3 Yancheng First People's Hospital, Yancheng, Jiangsu, China

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

    Background: Breast cancer, a major threat to women's health worldwide, has mechanisms of onset that remain unclear. Within the human lysosomal system, a class of enzymes known as cathepsins exhibit elevated expression levels in various malignant tumours, suggesting that they may play key roles in cancer progression. Methods: This study employed the two-sample Mendelian randomization (MR) approach to investigate the potential causal relationship between cathepsin levels and the risk of developing breast cancer. Furthermore, we conducted MR analysis using eQTL data to investigate how gene expression, mediated by cathepsins, affects the occurrence of different types of breast cancer and assessed the regulatory effects of cathepsins. Results: MR analysis revealed that increased levels of cathepsin E are associated with a greater risk of malignant breast tumours (IVW: p = 0.006, OR = 1.103, 95% CI = 1.028-1.184), and increased levels of cathepsin F are associated with an increased risk of in situ breast cancer (IVW: p = 0.031, OR = 1.190, 95% CI = 1.016-1.394). Additionally, cathepsin Z has a protective effect against in situ breast cancer (IVW: p = 0.017, OR = 0.846, 95% CI = 0.737-0.971). Cathepsin E can mediate the effects of APBB1IP, NT5C3B, and ZNF66 on HER2-negative breast cancer, as well as the effects of DHRS9, CDK12, and CD247 on HER2-positive breast cancer. Cathepsin F can mediate the effects of ANXA2R and ZNF605 on in situ breast cancer. Cathepsin Z can mediate the effects of PRX, CRY2, ADCY3, and PELATON on in situ breast cancer. Discussion: These findings highlight the dual roles of cathepsins as potential risk and protective factors for breast cancer, underscoring their potential in diagnostic and therapeutic strategies.

    Keywords: Mendelian randomization, Cathepsin, breast cancer, mediation effect, eQTL analysis

    Received: 28 Mar 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Zhou, Sun, Zha and Zhou. 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:
    Shengyi Zhou, School of Medicine, Xiamen University, Xiamen, 361102, Fujian, China
    Wenzhang Zha, Yancheng First Hospital，Affiliated Hospital of Nanjing University Medical School, Yancheng, China
    Guangjun Zhou, Yancheng First People's Hospital, Yancheng, 224001, Jiangsu, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.