Peng Tuo, Li Tian, Zhang Caihua
Department of Urology, People's Hospital Affiliated to Chongqing Three Gorges Medical College, 27 Guoben Rd, Chongqing 404100, China.
Tianjin Key Laboratory of Acute Abdomen Disease-Associated Organ Injury and ITCWM Repair, Institute of Integrative Medicine of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin Medical University, 8 Changjiang Avenue, Tianjin 300100, China.
Postgrad Med J. 2025 Jan 16. doi: 10.1093/postmj/qgaf003.
Previous studies have established a relationship between cathepsins and renal cancer. Nonetheless, the specific causal connection between the two factors continues to be ambiguous. The aim of this study is to evaluate the causal relationship between cathepsins and renal cancer via employing Mendelian randomization (MR).
The summary data of genome-wide association study were used for univariable MR (UVMR), reverse MR, and multivariable MR (MVMR) analyses. The primary MR method used in this study was Inverse variance weighting.
UVMR analysis showed that cathepsin Z increased the overall risk of renal cancer and cathepsin F were observed increased the risk of clear cell renal cell carcinoma. Furthermore, the concentration of cathepsin S had a significant positive correlation with the risk of papillary renal cell carcinoma (pRCC), whereas that of cathepsin G was negatively correlated with the risk of pRCC. Reverse MR analysis showed that renal cancer reduced the concentration of cathepsin H. MVMR analysis showed that the concentration of cathepsin B had a significant positive correlation with overall risk of renal cancer and pRCC. In addition, a higher concentration of cathepsin S was significantly associated with an increased risk of pRCC.
This study confirmed a direct link between cathepsins and the risk of renal cancer. Specifically, cathepsin S has a significant positive correlation with the risk of pRCC. The findings of our research could provide significant contributions to both fundamental and clinical investigations pertaining to renal cancer. Key message What is already known on this topic? - Previous studies have suggested the role of some cathepsins in renal cancer occurrence and progression. However, the causal link between different cathepsins and renal cancer is unknown. What this study adds? - Our Mendelian randomization (MR) study revealed that the effects of different cathepsins on the risk of renal cancer. Remarkably, both univariable MR and multivariable MR demonstrated that the levels of cathepsin S increases the risk of papillary renal cell carcinoma. How this study might affect research, practice or policy? - The findings offer novel insights into the relationship between cathepsins and renal cancer, which may have implications for the prevention and management of renal cancer.
既往研究已证实组织蛋白酶与肾癌之间存在关联。尽管如此，这两个因素之间的具体因果关系仍不明确。本研究旨在通过孟德尔随机化（MR）评估组织蛋白酶与肾癌之间的因果关系。
采用全基因组关联研究的汇总数据进行单变量MR（UVMR）、反向MR和多变量MR（MVMR）分析。本研究使用的主要MR方法是逆方差加权法。
UVMR分析显示，组织蛋白酶Z增加了肾癌的总体风险，组织蛋白酶F增加了透明细胞肾细胞癌的风险。此外，组织蛋白酶S的浓度与乳头状肾细胞癌（pRCC）的风险呈显著正相关，而组织蛋白酶G的浓度与pRCC的风险呈负相关。反向MR分析显示，肾癌降低了组织蛋白酶H的浓度。MVMR分析显示，组织蛋白酶B的浓度与肾癌和pRCC的总体风险呈显著正相关。此外，组织蛋白酶S浓度较高与pRCC风险增加显著相关。
本研究证实了组织蛋白酶与肾癌风险之间的直接联系。具体而言，组织蛋白酶S与pRCC风险呈显著正相关。我们的研究结果可为肾癌的基础研究和临床研究做出重大贡献。关键信息 关于该主题已知的信息有哪些？- 既往研究提示了一些组织蛋白酶在肾癌发生和进展中的作用。然而，不同组织蛋白酶与肾癌之间的因果联系尚不清楚。本研究补充了什么？- 我们的孟德尔随机化（MR）研究揭示了不同组织蛋白酶对肾癌风险的影响。值得注意的是，单变量MR和多变量MR均表明，组织蛋白酶S水平增加了乳头状肾细胞癌的风险。本研究可能如何影响研究、实践或政策？- 这些发现为组织蛋白酶与肾癌之间的关系提供了新的见解，可能对肾癌的预防和管理具有重要意义。
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