PTCH1 gene variants rs357564, rs2236405, rs2297086 and rs41313327, mRNA and tissue expression in basal cell carcinoma patients from Western Mexico

Abstract

BackgroundBasal cell carcinoma (BCC) represents about 80% of all cases of skin cancer. The PTCH1 is a transmembrane protein of the Sonic Hedgehog signaling pathway that regulates cell proliferation. Genetic variants in PTCH1 gene have been previously described in association with BCC development. In addition, PTCH1 mRNA and protein expression analysis are also significant to understand its role in skin cancer physiopathology.MethodsAn analytical cross‐sectional study was performed, and a total of 250 BCC patients and 290 subjects from the control group (CG) were included, all born in western Mexico. The genotypes and relative expression of the mRNA were determined by TaqMan® assay. The protein expression was investigated in 70 BCC paraffin‐embedded samples with PTCH1 antibodies. Semi‐quantitative analysis was performed to determine the expression level in the immunostained cells.ResultsWe did not find evidence of an association between PTCH1 rs357564, rs2297086, rs2236405, and rs41313327 genetic variants and susceptibility to BCC. Likewise, no statistically significant differences were found in the comparison of the mRNA level expression between BCC and CG (p > 0.05). The PTCH1 protein showed a low expression in 6 of the analyzed samples and moderate expression in 1 sample. No association was found between genetic variants, protein expression, and demographic‐clinical characteristics (p > 0.05).ConclusionThe studied PTCH1 variants may not be associated with BCC development in the Western Mexico population. The PTCH1 mRNA levels were lower in patients with BCC compared to the control group, but its protein was underexpressed in the tissue samples.

PTCH1 Gene Variants, mRNA Expression, and Bioinformatics Insights in Mexican Cutaneous Squamous Cell Carcinoma Patients

“…PTCH1 variants rs357564, rs2236405, rs2297086, and rs41313327 were analyzed in the cSCC patients and the CG. The variants rs357564 and rs2236405 were found to conform to Hardy–Weinberg equilibrium (HWE), while rs2297086 and rs41313327 did not ( p < 0.05), according to previously published results for our control group [ 40 ]. This is related to the fact that only the major alleles of the rs2297086 (G) and rs41313327 (C) variants were present in all of the genotyped individuals.…”

“…The rs357564 and rs2236405 variants were found to be in moderate LD (D’ = 0.77, p = 0.0047), but there was no association between the haplotypes and the cSCC risk, consistent with our previous report in BCC [ 40 ]. As non-canonical mechanisms are known to activate HH signaling, it is plausible that other mechanisms are involved in the role of PTCH1 in tumorigenesis, not specifically related to these variants [ 12 ].…”