Immunohistochemical and bioinformatic analysis of pannexin-1 expression in cutaneous basal and cutaneous squamous cell carcinomas

Abstract

Objectives: In this two-center study, we aimed to evaluate PANX1 expression in cutaneous squamous cell carcinoma (SCC) and cutaneous basal cell carcinoma (BCC) and to investigate molecular pathways and biological differences associated with PANX1 expression in these tumor types. Methods: In this study, the biopsy samples obtained for pathological examination from patients diagnosed with SCC and BCC were analyzed. The histochemical and immunohistochemical characteristics of the samples were evaluated. Bioinformatics and molecular docking studies were conducted for further analysis. Results: Digital image analysis using immunohistochemical staining and H-score evaluation on paraffin-embedded tissues revealed that PANX1 expression was significantly higher in SCC cases compared to BCC (p<0.001). In SCC, prominent cytoplasmic and membranous staining was observed in invasive tumor foci, while weak and homogeneous staining was detected in BCC samples. Bioinformatic analyses revealed that PANX1 interacts with proteins such as CASP1, CASP3, and P2RX7. However, Venn diagram analysis showed that CASP3 is the only common gene interacting with PANX1 and associated with SCC. No overlap was detected with BCC. Furthermore, molecular docking analyses revealed that ATP binds to PANX1 with high affinity and that caspase-3 establishes a stable interaction near the DVVD cleavage site of PANX1. Conclusions: Our two-center study demonstrated that PANX1 expression is higher in SCC compared to BCC and may play a role in the invasive phenotype. Bioinformatic analyses support the idea that PANX1's interaction with CASP3 through inflammatory and apoptotic pathways may contribute to the progression of SCC. However, more comprehensive studies are needed to determine the diagnostic and prognostic value of PANX1. © 2026 the author(s), published by De Gruyter, Berlin/Boston.