Limitations of the commercially available gene expression test in predicting cutaneous squamous cell carcinoma metastasis and clinical outcomes

Joel L Sax; Christopher D McFarland; Bryan T Carroll

doi:10.1016/j.jaad.2024.05.014

Limitations of the commercially available gene expression test in predicting cutaneous squamous cell carcinoma metastasis and clinical outcomes

J Am Acad Dermatol. 2024 May 16:S0190-9622(24)00746-1. doi: 10.1016/j.jaad.2024.05.014. Online ahead of print.

Authors

Joel L Sax¹, Christopher D McFarland¹, Bryan T Carroll²

Affiliations

¹ Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio.
² Department of Dermatology, Case Western Reserve University School of Medicine, Cleveland, Ohio; Department of Dermatology, University Hospitals, Cleveland, Ohio. Electronic address: Bryan.Carroll@uhhospitals.org.

PMID: 38762012
DOI: 10.1016/j.jaad.2024.05.014

Abstract

Background: Clinical genetic tests are integral to healthcare decision-making.

Objective: To critically evaluate the DecisionDx cutaneous squamous cell carcinoma test by Castle Biosciences for its dataset biases, gene panel selection, and reported accuracy metrics, providing insight into broader challenges in the clinical genetic testing landscape.

Methods: Independent analyses of the DecisionDx-SCC 40-GEP test data from Castle Biosciences were conducted. These included comparisons to clinical genetic testing standards, analysis of prevalence metrics against national cutaneous squamous cell carcinoma (cSCC) rates, gene ontology of 34 genes for cSCC associations, and evaluation of accuracy metrics.

Results: The DecisionDx-SCC dataset showed a metastasis prevalence higher than the national average. Out of 34 genes, 15 had known associations with cSCC. Inconsistencies in the presentation of accuracy metrics were noted, particularly in moderate and high-risk stratifications.

Conclusion: Analysis of DecisionDx-SCC indicates potential biases and ambiguities. This highlights the need for systematic validation, stressing the necessity for precise and dependable genetic testing in patient care.

Keywords: cancer biology; clinical genetics; cutaneous squamous cell carcinoma; dermatology; gene expression; genomics.