Spatial transcriptomics identified LGACC specific signature

Abstract

Purpose : Lacrimal gland adenoid cystic carcinoma is a rare, very lethal cancer originating in the cells of secretory glands. The only life extending technique for ACC patients is to remove the eye and surrounding socket contents entirely. ACC, although very slow growing, is an aggressive cancer with a 10-year survival rate of 20%, even with radical treatment. Most patients will present with metastatic disease to the brain, lung, liver, or bones several years out from initial diagnosis and before symptoms are noticeable. Due to the rarity of LGACC, it is not well understood leading to difficulty in diagnosing, treating, and monitoring disease progression. Here, we aim to further understand the molecular drivers of LGACC and discover novel targets for specifically treating LGACC.

Methods : We have conducted RNA sequencing, mass spectrometry, and spatial transcriptomics to further understand the molecular signatures of LGACC. We performed differential gene expression, gene ontology, and pathway analysis for each assay and compared the signatures found in the RNA sequencing and mass spectrometry to the spatial transcriptomics to identify a specific LGACC signature.

Results : Our analysis identified important biological processes and pathways that drive LGACC progression, most significantly the extracellular matrix, collagen catabolic processes, and cell and focal adhesion. In comparing our bulk sequencing analysis to our spatial transcriptomics, we have found LGACC-specific transcriptomic signatures that had not yet been identified with specificity to the tumor. This allowed us to identify the gene signature specific to LGACC apart from the surrounding supportive tissue.

Conclusions : With this extensive analysis of the molecular signatures, we now have a deeper understanding of the drivers of this slow-growing, lethal cancer. This analysis lays the groundwork for the development of reliable molecular diagnostics, prognostics, and surveillance assays as well as therapies specifically targeting differential expression signatures.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.