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.

Keratinocyte Cytokine Networks Associated with Human Melanocytic Nevus Development

“…As previously mentioned, some BCCs are pigmented. To study gene expression associated with melanocyte activation in this context, we used gene expression data from a human BCC cohort (Jee et al, 2015). Gene expression networks were constructed at a confidence value of 0.9 using STRING (https://string-db.org) for human abdomen and leg skin and BCC (Figure 1eeg).…”

Altered Expression of PRKX, WNT3 and WNT16 in Human Nodular Basal Cell Carcinoma

“…Several lines of evidence implicate cross-talk between the WNT and HH pathways in tumorigenesis and suggest their involvement in progression to aggressive, invasive, and metastatic disease stages (3,16,23,24). Scant data have been published regarding gene involvement in either nodular or superficial BCC tumors and no extensive analysis of gene expression modulation exists (3, 4, 13, 25).…”

“…differences in their biological behavior, such as tumor growth pattern, potential for recurrence and metastasis, histological pattern and genetic factors. In addition, it is important to consider extrinsic factors, such as site of origin, therapeutic choice and immunological state of the person with the tumor (3). Nodular BCC is the most common biopsied subtype; it usually manifests as a single lesion and mostly affects head and neck areas (8).…”

“…WNT and HH have gained notorious attention in skin cancer, especially in BCC. The HH signaling pathway is known to be activated in most BCCs and mutations in HH genes, especially Patched 1 (PTCH1) and Smoothened, frizzled class receptor (SMO), are pivotal to the development of BCC (3,12,13). Target genes in which expression is up-regulated directly by HH signaling are PTCH1, GLI family zinc finger 1 (GLI1), GLI2, protein kinase cAMP-activated catalytic subunit alpha (PRKACA) and hedgehog-interacting protein (HHIP) (2,4,14).…”

069 Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma

“…Gene expression analysis. Processed gene-expression data for BCC and normal skin (GSE53462 and GSE7553) were obtained from the GEO (http://www.ncbi.nlm.nih.gov/geo/) [71][72][73] . Fifteen BCC samples and five controls were included for GSE7553; for GSE53462, nine 'classic-type' BCC samples were included, along with five controls.…”