222P - Features of epithelial-to-mesenchymal transition (EMT) and humoral immune response in ulcerated acral melanoma: A transcriptomic and spatial proteomic analysis.

Background

Acral melanoma (AM) is a subtype of melanoma that develops in hairless skin such as hand palms, foot soles, and beneath nails (Saida et al., 2018). This melanoma subtype is characterized for its unfavourable prognosis (Lino Silva et al., 2016) and lack of effective treatment options (Mao et al., 2021). Ulceration is a crucial prognostic indicator, associated with increased risk of brain metastasis and recurrence (Namikawa et al., 2018; Koeblinger et al., 2019). While patients with ulceration are reported to benefit from interferon therapy, the underlying molecular mechanisms remain elusive.

Methods

We employed transcriptome sequencing through exome-capture bulk RNA-sequencing on 65 primary tumors from 64 Mexican patients, alongside spatial protein profiling on 110 tumor segments from 45 patients. These samples were collected from the National Cancer Institute of Mexico and were annotated with vast clinical information.

Results

Our research uncovered a significant upregulation of immunoglobulin-associated transcripts in ulcerated acral tumours. These lesions exhibited increased plasma cell infiltration, B cell signaling activity, and epithelial-mesenchymal transition (EMT) characteristics. Protein-level validation confirmed an inflammatory profile and decreased fibronectin abundance. Utilizing a Random Forest classifier, we identified a subset of proteins with predictive power for distinguishing ulcerated from non-ulcerated acral tumours.

Conclusions

Our study identified genes, proteins, and immune cell types potentially driving a dysregulated immune response and tumour-promoting inflammation in ulcerated acral lesions. These analyses enhance our comprehension of the ulcerated phenotype, advancing our knowledge of the altered components of the tumour microenvironment in an understudied disease.

Legal entity responsible for the study

The authors.

Funding

CONAHCYT, Wellcome Trust, Melanoma Research Alliance.

Disclosure

D. Adams: Non-Financial Interests, Institutional, Speaker, Consultant, Advisor: Microbiotica. All other authors have declared no conflicts of interest.