Gene expression changes of angiogenesis factors during basal skin cancer laser destruction

Abstract

Background. Basal cell carcinoma is the most widespread malignant skin neoplasm. Angiogenesis is critical for the growth and metastasis of malignant tumors. Aims. To study the levels of representation of transcripts in the foci of basal cell skin cancer before and after the therapy of genes for angiogenesis proteins and their receptors: angiopoietin 2 ANGPT2, calcitonin-related polypeptide alpha CALCA, epidermal growth factor receptor EGRF, fibroblast growth factor FGF2, intracellular adhesion molecule ICAM1, vascular endothelial growth factor VEGFA and its type 2 receptor VEGFR2, matrix metalloproteinase MMP9, homologue protein of phosphatase and tensin PTEN, tachykinin receptor TAC1, and tumor necrosis factor protein genes TNF. Methods. The study included 31 patients with histologically confirmed basal cell skin cancer who received treatment at the consultative and diagnostic center of the State Research Center of Dermatovenereology and Cosmetology of Russian Ministry of Health, Moscow in the period from 2020 to 2021, using a pulsed dye laser (wavelength — 585 nm) and long-pulsed neodymium laser (wavelength — 1064 nm). The patients provided skin punch biopsies from BCC lesions and after therapy from the same localization. The gene expression was analyzed with real-time reverse transcription PCR using endogeneous control, and the gene expression ration changes during the therapy were calculated according to Livak’s double delta formulae. Results. An increased expression of the matrix metalloproteinase MMP9 and the tachykinin precursor TAC1 genes were revealed in skin biopsy samples of the superficial form of basal cell skin cancer during laser pulsed therapy. The expression of tumor necrosis factor TNF, epidermal growth factor receptor EGFR, fibroblast growth factor FGF2 genes increases to a lesser extent. The increasing expression of MMP9 and TAC1 genes also established in skin biopsy samples of the nodular form of basal cell skin cancer. It was shown that the expression of the calcitonin-related polypeptide alpha CALCA gene in the skin of patients is at basal level, which makes it possible to exclude the influence of the neuropeptide on the basal cell skin cancer pathogenesis. Despite the bidirectional changes in expression due to individuality of patients, the average values allow to conclude the expression of all the studied genes is increased after pulse laser destruction therapy. This means neoangiogenesis is continued at the skin even after the destruction of basal cell skin cancer lesions. This could be due to the presence of the basal cell carcinoma microenvironment, likely mast cells, at the affected skin area. Conclusions. Among the factors of neoangiogenesis potentially influencing the development of basal cell skin cancer, the leading role of expression of the MMP9 matrix metalloproteinase and TAC1 precursor protein of tachykinin has been shown. Simultaneous changes in the level of these proteins may be due to neuroimmune interactions in the epidermis, which is probably realized by mast cells as the microenvironment of the basal cell carcinoma. In the process of laser destruction, there is also a slightly pronounced increased expression of additional factors of neoangiogenesis.