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

Cutaneous squamous cell carcinoma (cSCC) is a common skin malignancy, in which immune dysregulation plays a pivotal role in driving disease progression and therapy resistance. Centrosomal amplification (CA), a marker of genomic instability, promotes cancer development by disrupting essential biological processes, including cell division, immune activation, antigen presentation, and cytokine signaling. Therefore, exploring the interaction between centrosomal alterations and immune regulation may reveal new therapeutic targets, thereby improving diagnostic and treatment approaches for cSCC. Centrosomal and immune-related biomarkers for cSCC were identified by screening public databases using 101 combinatorial models derived from 10 machine learning algorithms. Subsequent RT-qPCR validation was complemented by artificial neural network (ANN) analysis to evaluate the diagnostic potential of these candidate biomarkers. The underlying mechanisms of the identified biomarkers were further explored through enrichment analysis, immune infiltration profiling, and single-cell RNA sequencing. Two biomarkers, BIRC5 and HDAC1, were identified. Both are primarily expressed in epithelial cells and demonstrate significant diagnostic potential for cSCC. These molecules are closely associated with the cell cycle and immune checkpoints, particularly CD276. Single-cell RNA sequencing revealed eight distinct epithelial cell types, with BIRC5 and HDAC1 exhibiting the highest expression levels, suggesting their involvement in cSCC development by affecting epithelial cell function during tumor initiation and progression. This study identifies BIRC5 and HDAC1 as important biomarkers that facilitate centrosome-immune communication, offering promising targets for accurate diagnosis and treatment strategies in cSCC management.