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Background <p>Cervical cancer is the fourth most common cancer affecting the female reproductive system worldwide. Although several studies have reported recurrent mutations in cervical squamous cell carcinoma (SCC), a comprehensive understanding of the clinically relevant driver genes remains limited. Unlike previous single-cohort or frequency-based reports, this study integrates four independent cervical squamous cell carcinoma (SCC) cohorts with network-based analysis, multiendpoint survival assessment, and drug–gene interaction to prioritize functionally and clinically relevant driver hub genes.</p> Materials and methods <p>In this study, we performed a genomic analysis of a cohort of 4 squamous cell carcinomas of the cervix (SCCs), consisting of 467 samples, to identify driver genes and their clinical significance. Key pathways and biological functions affected were tested by functional enrichment analysis. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and CytoHubba tools were used to construct a protein‒protein interaction network (PPIN) and identify the hub genes. Additional analyses included enrichment assessment of cancer hallmarks, survival evaluation, immune cell infiltration profiling, and drug‒gene interaction studies.</p> Results <p>Our analysis revealed 9,749,109 mutations across 44 driver genes. <i>PIK3CA</i>,<i> KMT2C</i>,<i> KMT2D</i>,<i> FBXW7</i>,<i> FAT1</i>,<i> EP300</i>,<i> TP53</i>,<i> NOTCH1</i>,<i> STK11</i>, and <i>CASP8</i> were the top 10 mutated genes. <i>PIK3CA</i>,<i> NOTCH1</i>,<i> PTEN</i>,<i> KRAS</i>,<i> ERBB2</i>,<i> TP53</i>,<i> ARID1A</i>,<i> EP300</i>,<i> STK11</i>, and <i>FBXW7</i> emerged as the top 10 hub genes according to the results of the PPIN and Cytohubba analyses. In addition, we observed significant differences in T helper cell type 2, natural killer cell, dendritic cell, and gamma delta T-cell composition in samples with hub gene mutations. Prioritization analysis of drug and hub gene interactions revealed 112 clinically relevant compounds, especially HER2-directed therapies (trastuzumab), PI3K inhibitors (alpelisib), and mTOR inhibitors (everolimus).</p> Conclusion <p>Collectively, our analysis describes the driver genes and mutation characteristics in SCC. The multi-cohort and network-based framework employed in this study identifies candidate hub genes that warrant further clinical investigation in cervical cancer.</p>

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In silico analysis of driver genes in squamous cell carcinoma of the cervix: insights into their biological functions, prognosis, immune infiltration, and therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月1日

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  • Samatha Bhat,
  • Vasudha Devi,
  • Shama Prasada Kabekkodu

摘要

Background

Cervical cancer is the fourth most common cancer affecting the female reproductive system worldwide. Although several studies have reported recurrent mutations in cervical squamous cell carcinoma (SCC), a comprehensive understanding of the clinically relevant driver genes remains limited. Unlike previous single-cohort or frequency-based reports, this study integrates four independent cervical squamous cell carcinoma (SCC) cohorts with network-based analysis, multiendpoint survival assessment, and drug–gene interaction to prioritize functionally and clinically relevant driver hub genes.

Materials and methods

In this study, we performed a genomic analysis of a cohort of 4 squamous cell carcinomas of the cervix (SCCs), consisting of 467 samples, to identify driver genes and their clinical significance. Key pathways and biological functions affected were tested by functional enrichment analysis. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and CytoHubba tools were used to construct a protein‒protein interaction network (PPIN) and identify the hub genes. Additional analyses included enrichment assessment of cancer hallmarks, survival evaluation, immune cell infiltration profiling, and drug‒gene interaction studies.

Results

Our analysis revealed 9,749,109 mutations across 44 driver genes. PIK3CA, KMT2C, KMT2D, FBXW7, FAT1, EP300, TP53, NOTCH1, STK11, and CASP8 were the top 10 mutated genes. PIK3CA, NOTCH1, PTEN, KRAS, ERBB2, TP53, ARID1A, EP300, STK11, and FBXW7 emerged as the top 10 hub genes according to the results of the PPIN and Cytohubba analyses. In addition, we observed significant differences in T helper cell type 2, natural killer cell, dendritic cell, and gamma delta T-cell composition in samples with hub gene mutations. Prioritization analysis of drug and hub gene interactions revealed 112 clinically relevant compounds, especially HER2-directed therapies (trastuzumab), PI3K inhibitors (alpelisib), and mTOR inhibitors (everolimus).

Conclusion

Collectively, our analysis describes the driver genes and mutation characteristics in SCC. The multi-cohort and network-based framework employed in this study identifies candidate hub genes that warrant further clinical investigation in cervical cancer.