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Deciphering the role of wound healing genes in skin cutaneous melanoma: Insights into expression, methylation, mutations, and therapeutic implications

Abstract

Skin Cutaneous Melanoma (SKCM) is a form of cancer that originates in the pigment-producing cells, known as melanocytes, of the skin. Delay wound healing is often correlated with the occurrence of and progression of SKCM. In this comprehensive study, we investigated the intricate roles of two important wound healing genes in SKCM, including Matrix Metalloproteinase-2 (MMP2) and Matrix Metalloproteinase-9 (MMP9). Through a multi-faceted approach, we collected clinical samples, conducted molecular experiments, including RT-qPCR, bisulphite sequencing, cell culture, cell Counting Kit-8, colony formation, and wound healing assays. Beside this, we also used various other databases/tools/approaches for additional analysis including, UALCAN, GEPIA, HPA, MEXPRESS, cBioPortal, KM plotter, DrugBank, and molecular docking. Our results revealed a significant up-regulation of MMP2 and MMP9 in SKCM tissues compared to normal counterparts. Moreover, promoter methylation analysis suggested an epigenetic regulatory mechanism. Validations using TCGA datasets and immunohistochemistry emphasized the clinical relevance of MMP2 and MMP9 dysregulation. Functional assays demonstrated their synergistic impact on proliferation and migration in SKCM cells. Furthermore, we identified potential therapeutic candidates, Estradiol and Calcitriol, through drug prediction and molecular docking analyses. These compounds exhibited binding affinities, suggesting their potential as MMP2/MMP9 inhibitors. Overall, our study elucidates the diagnostic, prognostic, and therapeutic implications of MMP2 and MMP9 in SKCM, shedding light on their complex interplay in SKCM occurrence and progression.

Influence of environmental risk factors on the development of wounds associated with squamous cell carcinoma

Abstract

The incidence of squamous cell carcinoma (SCC) is on the rise, making it a significant global health concern. Environmental risk factors are crucial to the development of SCC. This study sought to examine comprehensively the impact of these factors on the onset of SCC. We conducted a cross-sectional study involving 480 participants at Beijing tertiary care hospital. Utilizing structured questionnaires, data on demographics, environmental exposures, medical history and clinical characteristics were collected. The cohort was composed of 272 men (56.67%) and 208 women (43.33%). The majority (44.38%) were between ages of 41 and 60, and Type III skin predominated (34.79%). Most of the participants belonged to the middle socioeconomic class (60.83%). ‘Vegetarian’ dietary habits (46.67%) were prevalent, as was the ‘Sedentary’ lifestyle (49.79%). Regarding environmental exposures, moderate sun exposure of 3 to 5 h per day (54.58%) and UV protective eyewear (30.83%) were prevalent. The majority (69.58%) of respondents indicated ‘Never’ exposure to carcinogens. A variety of wound characteristics were observed, with ‘non-smokers’ (64.17%) dominating. Most SCC lesions were located on the extremities (40.21%), lasted less than 6 months (44.38%) and measured 1–3 cm (39.79%). The majority (54.58%) did not have a history of cutaneous injuries. Our research uncovered substantial relationships between SCC and numerous environmental variables, gender, Fitzpatrick skin type, occupation, duration of sun exposure, exposure to carcinogens, dietary practices, history of skin wounds, wound location, duration, size and depth were significantly associated with the onset of SCC. These results highlighted the complexity of SCC aetiology and need for individualized prevention and treatment strategies.

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