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UV biomarker genes for classification and risk stratification of cutaneous actinic keratoses and squamous cell carcinoma subtypes
Author(s) -
Queen Dawn,
Shen Yao,
Trager Megan H.,
Lopez Adriana T.,
Samie Faramarz H.,
Lewin Jesse M.,
Niedt George W.,
Geskin Larisa J.,
Liu Liang
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001412r
Subject(s) - actinic keratoses , risk stratification , basal cell , dermatology , biomarker , actinic keratosis , medicine , molecular biomarkers , cancer research , oncology , biology , genetics
Currently, there is no sensitive molecular test for identifying transformation‐prone actinic keratoses (AKs) and aggressive squamous cell carcinoma (SCC) subtypes. Biomarker‐based molecular testing represents a promising tool for risk stratifying these lesions. We evaluated the utility of a panel of ultraviolet (UV) radiation‐biomarker genes in distinguishing between benign and transformation‐prone AKs and SCCs. The expression of the UV‐biomarker genes in 31 SCC and normal skin (NS) pairs and 10 AK/NS pairs was quantified using the NanoString nCounter system. Biomarker testing models were built using logistic regression models with leave‐one‐out cross validation in the training set. The best model to classify AKs versus SCCs (area under curve (AUC) 0.814, precision score 0.833, recall 0.714) was constructed using a top‐ranked set of 13 UV‐biomarker genes. Another model based on a 15‐gene panel was developed to differentiate histologically concerning from less concerning SCCs (AUC 1, precision score 1, recall 0.714). Finally, 12 of the UV‐biomarker genes were differentially expressed between AKs and SCCs, while 10 genes were uniquely expressed in the more concerning SCCs. UV‐biomarker gene subsets demonstrate dynamic utility as molecular tools to classify and risk stratify AK and SCC lesions, which will complement histopathologic diagnosis to guide treatment of high‐risk patients.