背景:已经确定几种组织蛋白酶与癌症的发展有关。然而,组织蛋白酶和皮肤癌之间的联系仍然非常难以捉摸。
方法:进行了双向孟德尔随机化(MR)分析,以研究组织蛋白酶与皮肤恶性肿瘤之间的因果关系。组织蛋白酶的全基因组关联研究(GWAS)数据,恶性黑色素瘤(MM),基底细胞癌(BCC)来自欧洲研究。采用的主要方法是逆方差加权。此外,MR-Egger,加权中位数,加权模式,和简单的模式也被执行。使用CochranQ检验进行敏感性分析,MR-Egger,MR-PRESSO
结果:来自单变量MR(UVMR),组织蛋白酶H,S与BCC有因果关系。此外,组织蛋白酶H被鉴定为与MM相关。多变量MR(MVMR)显示,纠正皮肤癌的危险因素后,检测到组织蛋白酶H对BCC具有保护作用,而组织蛋白酶S被观察为BCC的危险因素。在敏感性分析中没有发现实质性的多效性和异质性。
结论:这项研究首次建立了组织蛋白酶与皮肤恶性肿瘤之间的直接联系。组织蛋白酶H和S有可能作为BCC的新生物标志物,在及时识别中提供宝贵的帮助,治疗,和预防疾病。然而,我们还需要更多的临床试验来验证我们的发现.
BACKGROUND: Several cathepsins have been identified as being involved in the development of cancer. Nevertheless, the connection between cathepsins and skin cancers remained highly elusive.
METHODS: A bidirectional Mendelian randomization (MR) analysis was performed to investigate the causal association between cathepsins and skin malignancies. The genome-wide association studies (GWAS) data for cathepsins, malignant melanoma (MM), and basal cell carcinoma (BCC) were obtained from European research. The primary method employed was inverse variance weighted. In addition, MR-Egger, weighted median, weighted mode, and simple mode were also executed. Sensitivity analysis was performed using Cochran\'s Q test, MR-Egger, and MR-PRESSO.
RESULTS: From univariable MR (UVMR), cathepsin H, and S were determined to have a causal relationship with BCC. Additionally, cathepsin H was identified as associated with MM. Multivariable MR (MVMR) showed that after correcting for risk factors of skin carcinoma, cathepsin H was detected to be protective against BCC, whereas cathepsin S has been observed as a risk factor for BCC. No substantial pleiotropy and heterogeneity were identified in the sensitivity analysis.
CONCLUSIONS: This study was the first to establish a direct link between cathepsins and skin malignancies. Cathepsin H and S have the potential to serve as new biomarkers for BCC, offering valuable assistance in the prompt identification, treatment, and prevention of the disease. Nevertheless, additional clinical trials are required to validate our findings.