Identified BIRC5 and HDAC1 as Novel Diagnostic Biomarkers Linked to Centrosome-Immune Crosstalk for Cutaneous Squamous Cell Carcinoma via Machine Learning-Based Multi-omics Analysis

Background Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer where immune dysregulation plays a critical role in its progression and resistance to therapy. Centrosomal amplification (CA), a marker of genomic instability, contributes to cancer development by affecting cell division, immune cell activation, antigen presentation, and cytokine signaling. Further research into the interaction between centrosomal alterations and immune regulation could reveal new therapeutic targets and improve diagnosis and treatment strategies for cSCC. Methods Centrosomal- and immune-related signature biomarkers of cSCC were screened from public databases using 101 combinatorial models based on 10 machine learning algorithms, followed by RT-qPCR for validation and artificial neural networks (ANN) to assess the diagnostic efficacy of these biomarkers. Functional mechanisms were explored by enrichment analysis, immune infiltration profiling, and single-cell RNA sequencing. Results Two biomarkers, BIRC5 and HDAC1, were identified. They were mainly expressed in epithelial cells and both showed high diagnostic value for cSCC. These biomarkers were significantly related to the cell cycle and immune checkpoints, and were especially correlated with CD276. Single-cell RNA sequencing identified eight cell types, with BIRC5 and HDAC1 showing the highest expression levels in epithelial cells, suggesting their potential role in cSCC pathogenesis by modulating epithelial cell function during tumor initiation and progression. Conclusion This study identified and validated two centrosome-immune crosstalk biomarkers, BIRC5 and HDAC1, that may serve as novel targets for precise diagnostic and therapeutic strategies in cSCC management.