biostudies-literatureHu CKey Research and Development Program of Heilongjiang ProvinceHeilongjiang Postdoctoral FundSTI2030-Major ProjectsNational Science and Technology Major ProgramChina Postdoctoral Science FoundationNational Natural Science Foundation of China9956https://www.ebi.ac.uk/biostudies/studies/S-EPMC12562883biostudies-literatureUnknown26(20)Melanoma shows heterogeneity across body sites like skin, acral skin, and the uvea, driven by molecular characteristics and genetic variations. However, comparative studies exploring the heterogeneity of melanoma across different anatomical sites remain limited, hindering a comprehensive understanding of its underlying biology. We proposed a research framework through bioinformatics to analyze the tumor ecosystems of cutaneous, acral, and uveal melanoma, from molecular characteristics to genetic variations at single-cell resolution. We found that oxidative phosphorylation (OXPHOS) is a critical driver of tumor cell evolution, with abnormal ribosomal gene and tumor suppressor expression observed in uveal melanoma (UM). Additionally, we screened for potential drug targets and drugs against tInternational journal of molecular sciencesDissecting Melanoma Ecosystem Heterogeneity from Molecular Characteristics to Genetic Variation at Single-Cell Resolution.PMC125628832021ZD02024002024ZD05305002024M7607092024ZX12C27U23A2016662172131LBH-Z2421062472131Li XHu COu QLi TYang KZhang YMi WQi BLi LYu HfalseDissecting Melanoma Ecosystem Heterogeneity from Molecular Characteristics to Genetic Variation at Single-Cell Resolution.Melanoma shows heterogeneity across body sites like skin, acral skin, and the uvea, driven by molecular characteristics and genetic variations. However, comparative studies exploring the heterogeneity of melanoma across different anatomical sites remain limited, hindering a comprehensive understanding of its underlying biology. We proposed a research framework through bioinformatics to analyze the tumor ecosystems of cutaneous, acral, and uveal melanoma, from molecular characteristics to genetic variations at single-cell resolution. We found that oxidative phosphorylation (OXPHOS) is a critical driver of tumor cell evolution, with abnormal ribosomal gene and tumor suppressor expression observed in uveal melanoma (UM). Additionally, we screened for potential drug targets and drugs against t2025-01-01T00:00:00Z2025 Oct2026-05-15T03:17:04.706Z2026-05-15T03:12:14.361ZS-EPMC125628834115525010.3390/ijms26209956