Identification of dysregulated genes in cutaneous squamous cell carcinoma

Abstract

Carcinogenesis is a multi-step process resulting from the accumulation of genetic mutations and subsequently leading to dysregulated genes, but the number and identity of differentially expressed genes in cutaneous squamous cell carcinoma (SCC) is unknown at present. In order to identify dysregulated genes, we examined the relative mRNA expression present in cutaneous SCC and its precursor lesion actinic keratosis (AK) by comparison to normal skin. Snap frozen biopsies from 20 specimens of normal skin, 10 AK, and 10 cutaneous SCC were examined. Total-RNA was extracted, reversely transcribed, and 14 genes were investigated using gene-specific intron-flanking primers and quantitative real-time reverse transcription PCR. Specificity was confirmed by sequencing of the PCR amplicons. Ten of 14 genes were significantly dysregulated in AK and/or cutaneous SCC by comparison to normal skin. The genes CNN2, COX4I1, COX5B, COX7C, CRLF3, CTSC, NDRG1, and LMNA showed increased expression in skin cancer (p<0.02), while RPL15 and LGTN were down-regulated (p<0.03). The genes differentially expressed during skin carcinogenesis may prove useful in order to understand the origin and progression of cutaneous SCC and for diagnostic approaches.

In Silico Analysis Validates Proteomic Findings of Formalin-fixed Paraffin Embedded Cutaneous Squamous Cell Carcinoma Tissue

“…Several proteins found here to have higher abundances in cSCC tumor sections, were previously reported at higher levels in cSCC lesions using antibody-dependent methods, such as immunohistochemistry and western blots. Such proteins include TNC (12,25), IQGAP1 (51) and S100A2 (52). On the other hand, changes in proteins, such as S100A11, ANXA1, RPS8, RPS4X, FSCN1, MYH9, ARG1 and CST6, which play roles in various carcinogenic processes (53-60), were not previously reported in cSCC, and our study is the first to show such associations.…”

“…One of the most prominent contributing factors to poor patient outcome is the lack of sensitive biomarkers to facilitate early diagnosis and management of the tumor. A handful of genetic biomarkers have been studied in cSCC, including cellular tumor antigen p53 (TP53), notch 1 (NOTCH1) (6,7), human epidermal growth receptor 2 (HER2), HER4, E-cadherin (CDH1), epidermal growth factor receptor (EGFR), and podoplanin (PDPN) (5,8,9), and some have shown potential for prognostication (9)(10)(11)(12). However, there is a lack of evidence to recommend the use of these biomarkers for cSCC tumor stratification.…”

Systematical Analysis of Cutaneous Squamous Cell Carcinoma Network of microRNAs, Transcription Factors, and Target and Host Genes

“…Several genes involving the TP53 pathway, anti-apoptotic pathways, signal transduction, structural loss and DNA replication, including BCL2A1, MUC4, PTPN11 (SHP2) and FGF9, were confirmed upregulated in SCC and suggested to be warranted further study regarding their role in disease pathogenesis (Kathpalia et al, 2006). CNN2, COX4l1, COX5B, COX7C, CRLF3, CTSC showed increased expression (Dang et al, 2006). In cSCC.Matrix metallopeptidase 13 (MMP13) was identified as a direct target suppressed by miR-125b (Xu et al, 2012).…”

“…Analysis of IRF6 expression in a large series of SCCs showed a strong down-regulation that correlated with tumor invasive and differentiation status (Botti et al, 2011). RPL15 and LGTN were down-regulated and the expression of p15(INK4b) was significantly reduced (Dang et al, 2006;Moad et al, 2009). The expression of KGF receptor (KGFR) mRNA was lower in cutaneous SCCs than in normal skin samples (Toriseva et al, 2012).…”

The Clinicopathologic and Molecular Aspects of Non-Melanoma Skin Cancer

“…Several mRNA biomarkers for cSCC were identified, including CCR10, CCL27, MUC4, p16, MMP2 and MMP9. (61) A recent study has demonstrated that a distinct microRNA profile is modulated by UV radiation. (62) …”