In silico analysis of driver genes in squamous cell carcinoma of the cervix: insights into their biological functions, prognosis, immune infiltration, and therapy
The study identifies clinically relevant driver hub genes in cervical squamous cell carcinoma and highlights potential therapeutic targets, notably HER2-directed therapy (trastuzumab), PI3K inhibition (alpelisib), and mTOR inhibition (everolimus).
Cervical cancer is the fourth most common gynecological malignancy worldwide. While recurrent mutations have been reported in cervical squamous cell carcinoma (SCC), a comprehensive understanding of clinically relevant driver genes is lacking. Here we integrated four independent SCC cohorts (467 samples) for a multi‑cohort, network‑based analysis of driver genes, functional enrichment, survival assessment, immune infiltration profiling, and drug‑gene interactions. We identified 44 driver genes; the most frequently mutated were PIK3CA, KMT2C, KMT2D, FBXW7, FAT1, EP300, TP53, NOTCH1, STK11, and CASP8, while the top hub genes in the protein‑protein interaction network were PIK3CA, NOTCH1, PTEN, KRAS, ERBB2, TP53, ARID1A, EP300, STK11, and FBXW7. Immune infiltration analysis revealed differences in T helper 2, NK, dendritic, and gamma‑delta T‑cell subsets between hub‑gene mutant and non‑mutant tumors. Drug‑gene interaction screening yielded 112 clinically relevant compounds, particularly HER2‑directed therapy (trastuzumab), PI3K inhibitors (alpelisib), and mTOR inhibitors (everolimus). Our integrative framework highlights candidate hub genes that warrant further clinical investigation in cervical cancer.
Identifying driver hub genes in cervical squamous cell carcinoma provides actionable insights for precision oncology, informs prognostication, and suggests druggable targets that could improve therapeutic outcomes, especially given the limited efficacy of current standard regimens and the rising interest in targeted and immunotherapeutic approaches.
Evidence level: Állatkísérletes. Állatmodellben vizsgálták.
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