Association between cathepsins and skin cancers: A bidirectional two-sample Mendelian randomization study.

Area of Science:

• Oncology
• Genetics
• Biochemistry

Background:

• Cathepsins are implicated in various cancers, but their role in skin malignancies was unclear.
• This research addresses the elusive connection between cathepsins and skin cancers.

Purpose of the Study:

• To investigate the causal association between cathepsins and skin malignancies using Mendelian randomization.
• To identify potential biomarkers for skin cancer diagnosis and treatment.

Main Methods:

• A bidirectional Mendelian randomization (MR) analysis utilized genome-wide association studies (GWAS) data for cathepsins, malignant melanoma (MM), and basal cell carcinoma (BCC).
• Primary analysis employed inverse variance weighting, with MR-Egger, weighted median, weighted mode, and simple mode methods also used.
• Sensitivity analyses included Cochran's Q test, MR-Egger, and MR-PRESSO to assess pleiotropy and heterogeneity.

Main Results:

• Univariable MR indicated cathepsin H and S have a causal link with BCC, and cathepsin H with MM.
• Multivariable MR, after adjusting for risk factors, showed cathepsin H is protective against BCC, while cathepsin S is a risk factor for BCC.
• Sensitivity analyses found no significant pleiotropy or heterogeneity.

Conclusions:

• This study establishes a direct link between cathepsins and skin malignancies, specifically BCC and MM.
• Cathepsin H and S show potential as novel biomarkers for basal cell carcinoma, aiding in early detection, treatment, and prevention.
• Further clinical trials are necessary to validate these findings and their clinical utility.