Transcriptomic discovery of a theranostic signature (SERPINE1/MMP3/COL1A1/SPP1) for head and neck squamous cell carcinomas and identification of antrocinol as a candidate drug

Head and neck squamous cell carcinomas (HNSCC) are prevalent malignancies with a disappointing prognosis, necessitating the search for theranostic biomarkers for better management. Based on a meta-analysis of transcriptomic data containing ten clinical datasets of HNSCC and matched nonmalignant samples, we identified SERPINE1/MMP3/COL1A1/SPP1 as essential hub genes as the potential theranostic biomarkers. Our analysis suggests these hub genes are associated with the extracellular matrix, peptidoglycans, cell migration, wound-healing processes, complement and coagulation cascades, and the AGE-RAGE signaling pathway within the tumor microenvironment. Also, these hub genes were associated with tumor-immune infiltrating cells and immunosuppressive phenotypes of HNSCC. Further investigation of The Cancer Genome Atlas (TCGA) cohorts revealed that these hub genes were associated with staging, metastasis, and poor survival in HNSCC patients. Molecular docking simulations were performed to evaluate binding activities between the hub genes and antrocinol, a novel small-molecule derivative of an anticancer phytochemical antrocin previously discovered by our group. Antrocinol showed high affinities to MMP3 and COL1A1. Notably, antrocinol presented satisfactory drug-like and ADMET properties for therapeutic applications. These results hinted at the potential of antrocinol as an anti-HNSCC candidate via targeting MMP3 and COL1A1. In conclusion, we identified hub genes: SERPINE1/MMP3/COL1A1/SPP1 as potential diagnostic biomarkers and antrocinol as a potential new drug for HNSCC. •SERPINE1/MMP3/COL1A1/SPP1 hub gene drive the progression and invasive phenotype of HNSCC.•The hub gene predicts worse prognosis of HNSCC and therapy resistance.•The hub gene exhibited high frequencies of genetic and epigenetic alterations in HNSCC.•Antrocinol, a novel drug candidate has good pharmacokinetic properties.•Antrocinol demonstrated high potential for targeting MMP3 and COL1A1.