CDKN2A, ITGA3, SMAD4 and SIRT7 gene expression in human cutaneous squamous cell carcinoma development and pre-clinical diagnosis
摘要
Cutaneous squamous cell carcinoma (cSCC) is the second most frequent cause of skin cancer death after melanoma. An improved understanding of molecular mechanisms will likely contribute to the development of improved diagnostic and treatment strategies. We investigated changes in the expression of CDKN2A, ITGA3, SMAD4, and SIRT7 in human cSCC tumor tissue versus matched normal skin, and assessed their potential for use as diagnostic biomarkers.
MethodsStage T2 (AJCC-8) cSCC tumor and normal tissue were collected (n = 26), qPCR was performed to detect relative target gene expression, and ROC analysis was undertaken to investigate diagnostic power of these genes. The GENT2 and DepMap were used to compare target gene expression profiles in different human cancer tissues and cell lines, and a gene-gene interaction network was generated using GeneMANIA.
ResultsThe qPCR indicated an increase in ITGA3 (2.2-fold) and SIRT7 (1.5 fold), and a decrease in CDKN2A (-1.1 fold) and SMAD4 (-0.75) expression, in cSCC versus matched normal skin. The gene-gene interaction network showed co-expression of CDKN2A and SMAD4 and physical interactions between ITGA3 and SIRT7. ROC analysis indicated that target gene expression could efficiently discriminate cSCC from normal skin, supporting their potential use as diagnostic molecular biomarkers.
ConclusionsCDKN2A, ITGA3, SMAD4 and SIRT7 genes are involved in human cSCC development and have the potential for use as diagnostic molecular biomarkers; these findings should contribute to the development of novel diagnostic and therapeutic strategies.