title: Molecular classification of basal cell carcinoma of skin by gene expression profiling.
abstract: Non-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are more common kinds of skin cancer. Although these tumors share common pathological and clinical features, their similarity and heterogeneity at molecular levels are not fully elaborated yet. Here, by performing comparative analysis of gene expression profiling of BCC, SCC, and normal skin tissues, we could classify the BCC into three subtypes of classical, SCC-like, and normal-like BCCs. Functional enrichment and pathway analyses revealed the molecular characteristics of each subtype. The classical BCC showed the enriched expression and transcription signature with the activation of Wnt and Hedgehog signaling pathways, which were well known key features of BCC. By contrast, the SCC-like BCC was enriched with immune-response genes and oxidative stress-related genes. Network analysis revealed the PLAU/PLAUR as a key regulator of SCC-like BCC. The normal-like BCC showed prominent activation of metabolic processes particularly the fatty acid metabolism. The existence of these molecular subtypes could be validated in an independent dataset, which demonstrated the three subgroups of BCC with distinct functional enrichment. In conclusion, we suggest a novel molecular classification of BCC providing insights on the heterogeneous progression of BCC.
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Korea.|Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Korea.
authors.forename: Byul A
authors.initials: BA
authors.lastname: Jee
authors.affiliation: Department of Plastic and Reconstructive surgery, Hallym University Sacred Heart Hospital, Anyang, Korea.
authors.forename: Hyoseob
authors.initials: H
authors.lastname: Lim
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Korea.|Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Korea.
authors.forename: So Mee
authors.initials: SM
authors.lastname: Kwon
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Korea.|Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Korea.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Jo
authors.affiliation: Department of Plastic and Reconstructive Surgery, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Myong Chul
authors.initials: MC
authors.lastname: Park
authors.affiliation: Department of Plastic and Reconstructive Surgery, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Il Jae
authors.initials: IJ
authors.lastname: Lee
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hyun Goo
authors.initials: HG
authors.lastname: Woo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D053823:Hedgehog Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*
chemical_list: D053823:Hedgehog Proteins
keywords: basal cell carcinoma; gene expression profiling, heterogeneity; non-melanoma skin cancer; squamous cell carcinoma