Expression and prognostic value of cyclase-associated proteins in cutaneous melanoma

Weijie Ma; Jiexi Wen; Catherine Y Liu; Lorraine Zaki; Scott M Palisoul; Soma Jobbagy; Shaofeng Yan

doi:10.1097/CMR.0000000000001100

Expression and prognostic value of cyclase-associated proteins in cutaneous melanoma

Melanoma Res. 2026 Apr 21. doi: 10.1097/CMR.0000000000001100. Online ahead of print.

Authors

Weijie Ma^{1

2}, Jiexi Wen¹, Catherine Y Liu³, Lorraine Zaki⁴, Scott M Palisoul¹, Soma Jobbagy^{1

2}, Shaofeng Yan^{1

2}

Affiliations

¹ Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon.
² Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
³ University of Rochester School of Medicine and Dentistry, Rochester.
⁴ Touro College of Osteopathic Medicine, Middletown, New York, USA.

PMID: 42013053
DOI: 10.1097/CMR.0000000000001100

Abstract

Cyclase-associated proteins (CAP1 and CAP2) are conserved actin-regulatory proteins essential for cytoskeletal remodeling and cell motility. Their protein-level expression patterns and clinicopathologic significance in cutaneous melanoma remain poorly defined. CAP1 and CAP2 were evaluated via immunohistochemistry on a tissue microarray of benign nevi and cutaneous melanomas. Cytoplasmic staining in dermal melanocytes was scored (0-3; percentage and intensity). Public transcriptomic data were used to assess tumor stage-correlated mRNA levels. Functional annotation was performed using Search Tool for the Retrieval of Interacting Genes/Protein and Gene Ontology analyses, and survival was analyzed via Kaplan-Meier and Cox regression. CAP1/CAP2 mRNA was upregulated in melanoma versus bulk normal skin, with metastatic tumors exhibiting higher expression than primary tumors. Elevated expression also correlated with advanced tumor stage. CAP1 and CAP2 protein levels were significantly higher in melanomas than in benign nevi (P < 0.0001). In primary melanomas, elevated CAP1 and CAP2 expression scores correlated with adverse pathologic features, including increased Breslow depth, higher mitotic rate, and advanced T stage (P < 0.05). High expression of CAP1 (score = 3) and CAP2 (score ≥ 2) was significantly associated with shorter disease-specific survival (P = 0.0005 and P = 0.0055). While prognostic on univariate analysis, CAPs were not independent predictors in multivariate models. Network enrichment linked CAPs to actin dynamics, cyclic adenosine monophosphate-associated signaling, and cell morphogenesis. CAP1 and CAP2 are overexpressed in cutaneous melanoma and correlate with aggressive pathologic features and shorter survival, suggesting an association between CAP expression and cytoskeletal regulatory programs relevant to melanoma progression.

Keywords: benign nevus; cutaneous malignant melanoma; cyclase-associated protein; cyclase-associated protein 1; cyclase-associated protein 2; prognosis; survival; tissue microarray.