Muge Liu, Xiongsheng Xiao, Ling Jin, Siyi Li, Changwei Zheng, Zhengde Chen, Zhuoting Chen, Zhang Zhi
Department of Vascular and Thyroid Surgery, Affiliated Hospital of Guangdong Medical University, Guangdong, China.
Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Guangdong, China.
Endocr Metab Immune Disord Drug Targets. 2025 Jan 8. doi: 10.2174/0118715303305715240912172648.
Papillary Thyroid Carcinoma (PTC) is the most common thyroid cancer, with an etiology and progression that are not fully understood. Research suggests a link between cathepsins and PTC, but the causal nature of this link is unclear. This study uses Mendelian Randomization (MR) to investigate if cathepsins causally influence PTC risk.
We applied univariable and multivariable MR analyses using genetic variants as proxies for cathepsin levels. Genetic data for cathepsins were sourced from the INTERVAL study, while PTC data came from the Finnish Genome-Wide Association Study database. Our analysis employed several MR methods, including the Inverse Variance Weighted (IVW) approach, MR-Egger, and the Weighted Median method, to provide comprehensive insights and address possible pleiotropy.
MR findings suggest a significant causal association between higher cathepsin levels and increased PTC risk. Notably, genetic variants indicating higher cathepsin Z expression were positively causal associated with PTC risk (OR:1.1190, 95% CI: 1.0029-1.2486), multivariable analysis confirmed significant carcinogenesis role of cathepsin Z in PTC (OR: 1.1593, 95% CI: 1.0137-1.3258), with results consistent across various tests, indicating a robust relationship.
This study established a causal link between cathepsin levels and PTC risk, emphasizing the roles of cathepsin Z in its progression. These insights could lead to new therapeutic strategies targeting these enzymes. Further research is necessary to understand the underlying biological mechanisms and their clinical implications.
甲状腺乳头状癌（PTC）是最常见的甲状腺癌，其病因和进展尚未完全明确。研究表明组织蛋白酶与PTC之间存在联系，但这种联系的因果性质尚不清楚。本研究采用孟德尔随机化（MR）方法来探究组织蛋白酶是否对PTC风险有因果影响。
我们使用基因变异作为组织蛋白酶水平的代理，应用单变量和多变量MR分析。组织蛋白酶的基因数据来源于INTERVAL研究，而PTC数据来自芬兰全基因组关联研究数据库。我们的分析采用了几种MR方法，包括逆方差加权（IVW）法、MR-Egger法和加权中位数法，以提供全面的见解并解决可能的多效性问题。
MR结果表明，较高的组织蛋白酶水平与PTC风险增加之间存在显著的因果关联。值得注意的是，表明组织蛋白酶Z表达较高的基因变异与PTC风险呈正因果关联（OR：1.1190，95%CI：1.0029-1.2486），多变量分析证实组织蛋白酶Z在PTC中具有显著的致癌作用（OR：1.1593，95%CI：1.0137-1.3258），各项测试结果一致，表明存在稳健的关系。
本研究建立了组织蛋白酶水平与PTC风险之间的因果联系，强调了组织蛋白酶Z在其进展中的作用。这些见解可能会带来针对这些酶的新治疗策略。有必要进行进一步研究以了解潜在的生物学机制及其临床意义。
