Uveal Melanoma (UM), a highly aggressive and metastatic
intraocular
cancer with a strong propensity for liver metastasis, presents limited
therapeutic alternatives and unfavorable survival outcomes. Despite
its low incidence, the underlying mechanisms of UM pathogenesis and
the precise role of mitochondrial metabolism in UM remain inadequately
understood. Utilizing Cox proportional hazards regression analysis
was used to assess prognostic relevance, and consensus clustering
was employed for molecular subtyping. A risk signature was constructed
using Least Absolute Shrinkage and Selection Operator (LASSO) Cox
regression. We further conducted comparative analyses on clinicopathological
characteristics, somatic mutation profiles, drug sensitivity, gene
expression patterns, and tumor microenvironment features across different
molecular subtypes. Moreover, a nomogram was developed and evaluated.
Among 1234 mitochondria metabolism-related genes (MMRGs), 343 were
identified as significantly associated with the prognosis of UM. These
prognosis-associated MMRGs facilitated the classification of UM into
two distinct molecular subtypes, which displayed notable differences
in prognosis and pathological staging. Furthermore, an index termed
the MMRGs-derived index (MMI) was derived from eight MMRGs, serving
as a quantitative measure for poor prognosis risk in UM. MMI demonstrated
significant associations with clinicopathological characteristics,
somatic mutations, drug responsiveness, and the tumor microenvironment,
where higher MMI levels corresponded to worse prognosis, advanced
pathological stages, and increased immune cell infiltration. The nomogram
built upon MMI provided a potential tool for clinical prognosis assessment
in UM patients. This study demonstrated the potential value of MMRGs
in predicting prognosis and molecular stratification within UM; however,
additional clinical and basic research is warranted to validate their
applicability and elucidate the related mechanisms.
