This prospective, observational cohort study aims to explore the multi-omics profiles of liquid biopsies and develop clinical biomarkers in melanoma. Two hundred participants with pathologically confirmed acral or cutaneous melanoma who are scheduled to receive standard first-line immunotherapy will be enrolled. Blood samples will be collected at baseline and every 3 weeks during treatment, along with radiological assessments every 12 weeks. Tumor tissue will be obtained at surgery after approximately 3 months of therapy. Using microfluidic-based circulating tumor cell isolation, exosome enrichment, ctDNA analysis, and integrative multi-omics approaches, the study will compare molecular features across primary tumors, metastases, and liquid biopsy components. The primary outcomes are progression-free survival and overall survival, assessed up to 36 months. Secondary outcomes include changes in circulating tumor cell counts, ctDNA concentrations, exosomal biomarker levels, pathological response rate at surgery, and the predictive accuracy of a multi-omics model for treatment response. The findings are expected to provide a basis for personalized monitoring and treatment strategies in melanoma.

Inclusion Criteria:

• Diagnosed with acral or cutaneous melanoma according to the "Melanoma Diagnosis and Treatment Guidelines."
• Underwent sentinel lymph node biopsy with complete information available.
• Archived melanoma tissue samples available with complete information.
• Complete basic demographic and clinical information.
• Age 18-80 years, any sex.

Exclusion Criteria:

• Patients with severe organic diseases, immunodeficiency disorders, organ absence, or organ transplantation.
• Patients diagnosed with mucosal melanoma according to the "Melanoma Diagnosis and Treatment Guidelines."
• Patients with other concurrent malignant tumors (e.g., basal cell carcinoma, lung cancer).
• Incomplete patient information or pathological sample data.

Participants will be selected from outpatients and inpatients at the Department of Dermatology, Xijing Hospital. Eligible participants are male and female adults aged 18-80 years with histopathologically confirmed acral or cutaneous melanoma according to the Melanoma Diagnosis and Treatment Guidelines. All participants have undergone sentinel lymph node biopsy with complete information available, retain archived melanoma tissue samples, and are scheduled to receive standard first-line immunotherapy. Participants with mucosal melanoma, severe organ dysfunction, immunodeficiency, a history of other concurrent malignancies, or incomplete clinical data will be excluded.