Linking Megalin, Cubilin, Caveolin-1, GIPC1 and Dab2IP Expression to Ocular Tumorigenesis: Profiles in Retinoblastoma, Choroidal Melanoma, and the Normal Human Eye.
Higher CAV1 tumor expression is linked to worse survival in uveal melanoma
Linking Megalin, Cubilin, Caveolin-1, GIPC1 and Dab2IP Expression to Ocular Tumorigenesis: Profiles in Retinoblastoma, Choroidal Melanoma, and the Normal Human Eye.
Retinoblastoma (retinoblastoma) and uveal melanoma (uveal melanoma) remain vision-threatening and lethal ocular malignancies with limited molecular markers of differentiation state and prognosis.
We investigated whether proteins governing endocytosis and signaling, including Megalin (LRP2), Cubilin (cubilin), Caveolin-1, GAIP-interacting protein C-terminus 1 (GIPC1), and Disabled homolog 2-interacting protein (DAB2IP), exhibit subtype-specific expression patterns in ocular tumors and whether these patterns are related to transcriptomic profiles and survival.
Formalin-fixed, paraffin-embedded human ocular tissues included controls ( n = 10), retinoblastoma ( n = 10), and uveal melanoma subtypes (epithelioid, spindle, mixoid; total n = 30).
LRP2 expression was uniformly reduced across retinoblastoma and all uveal melanoma subtypes versus control.
CAV1 expression was increased in epithelioid melanoma but reduced in retinoblastoma, mixoid, and spindle melanomas.
GIPC1 and DAB2IP expression were preserved in epithelioid melanoma yet significantly reduced in retinoblastoma and mixoid/spindle melanomas.
GEO analyses revealed no significant differences for the five genes in uveal melanoma cell lines versus melanocytes (GSE62075).
Endocytic/signaling proteins exhibit distinct, subtype-linked expression in ocular tumors.
Integration with public datasets highlights CAV1 and GIPC1 as adverse survival correlates in uveal melanoma and positions LRP2/cubilin/DAB2IP dysregulation as features of ocular tumor biology, nominating candidate biomarkers and mechanistic targets.