IPTCH1/I Gene Variants, mRNA Expression, and Bioinformatics Insights in Mexican Cutaneous Squamous Cell Carcinoma Patients

• Published in: Biology (Basel, Switzerland) Switzerland), 2024-03, Vol.13 (3)
• Main Authors: Zambrano-Román, Marianela, Padilla-Gutiérrez, Jorge R, Valle, Yeminia, Muñoz-Valle, José Francisco, Guevara-Gutiérrez, Elizabeth, López-Olmos, Patricia Aidé, Sepúlveda-Loza, Laura Cristina, Bautista-Herrera, Luis Alberto, Valdés-Alvarado, Emmanuel
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis; Cancer; Computational biology; Development and progression; Genes; Genetic aspects; Melanoma; Messenger RNA; Oncology, Experimental; Skin; Skin cancer; Squamous cell carcinoma
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology13030191

Skin cancer represents a prevalent and significant global health concern. Our study focused on comprehending cutaneous squamous cell carcinoma in the Mexican population through the examination of genetic variants of the PTCH1 gene, the assessment of its mRNA’s relative expression, and the utilization of bioinformatics tools. Despite the absence of statistically significant associations in the experimental results, integrating bioinformatics was imperative to understand the impact of the analyzed variants on protein function, splicing, expression, and disease-related aspects. This contributes to our overarching comprehension of non-melanoma skin cancer development. Further investigation is crucial to gain a comprehensive understanding of the in vivo role of these genetic variants. Background: Skin cancer is one of the most frequent types of cancer, and cutaneous squamous cell carcinoma (cSCC) constitutes 20% of non-melanoma skin cancer (NMSC) cases. PTCH1, a tumor suppressor gene involved in the Sonic hedgehog signaling pathway, plays a crucial role in neoplastic processes. Methods: An analytical cross-sectional study, encompassing 211 cSCC patients and 290 individuals in a control group (CG), was performed. A subgroup of samples was considered for the relative expression analysis, and the results were obtained using quantitative real-time PCR (qPCR) with TaqMan[sup.®] probes. The functional, splicing, and disease-causing effects of the proposed variants were explored via bioinformatics. Results: cSCC was predominant in men, especially in sun-exposed areas such as the head and neck. No statistically significant differences were found regarding the rs357564, rs2236405, rs2297086, and rs41313327 variants of PTCH1, or in the risk of cSCC, nor in the mRNA expression between the cSCC group and CG. A functional effect of rs357564 and a disease-causing relation to rs41313327 was identified. Conclusion: The proposed variants were not associated with cSCC risk in this Mexican population, but we recognize the need for analyzing larger population groups to elucidate the disease-causing role of rare variants.