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Dryad

Spatial profiling of benign and malignant melanocytic tumors via RNA-SMI (CosMx)

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May 03, 2024 version files 7.80 GB

Abstract

Melanoma clinical outcomes emerge from incompletely understood genetic mechanisms operating within the tumor and its microenvironment. Here, we utilized single-cell RNA-based spatial molecular imaging (RNA-SMI) in patient-derived archival tumors to reveal clinically relevant markers of malignancy progression and prognosis. We examined spatial gene expression of 203,472 cells inside benign and malignant melanocytic neoplasms, including melanocytic nevi, primary invasive and metastatic melanomas. Algorithmic cell clustering paired with intratumoral comparative 2D-analyses visualized synergistic, spatial gene signatures linking cellular proliferation, metabolism, and malignancy, validated by protein expression. Metastatic niches included upregulation of CDK2 and FABP5, which independently predicted poor clinical outcome in 473 melanoma patients via Cox regression analysis. More generally, our work demonstrates a framework for applying single-cell RNA-SMI technology toward identifying gene regulatory landscapes pertinent to cancer progression and patient survival.