Spatial Transcriptomics Recontextualizes the Cellular Environment of Conjunctival Melanoma

Conjunctival melanoma (CM) is a rare cancer with a potentially high recurrence rate. The mechanics of its progression, its relationship with neighboring tissues, and its molecular characteristics are largely unknown. Diagnosis currently requires a biopsy and the time and expertise of a pathologist.

Archived human biopsies containing CM were submitted to Xenium spatial transcriptomic analysis. Regions were graded by disease progression through histopathology. Differential expression (DE) and composition analysis were performed across disease states.

From three patients, 12 formalin-fixed paraffin-embedded (FFPE) tissue specimens were recovered. Composition analysis showed that melanoma depletes fibroblast and epithelial cells while melanocytes proliferate. DE signatures specific to each state show a clear pattern of progression from inflammation, to cellular restructuring, and then to tumor progression and malignancy.

Spatial transcriptomics allows single-cell transcriptomics techniques to compare spatially relevant annotations that are difficult to separate by library. This study proposes disease progression biomarker candidates that may elucidate the mechanics of CM progression and function as objective diagnostic and prognostic tools in the future.