Deciphering oral cancer subtypes: Integrating differential gene expression and pathway analysis followed by non-negative matrix factorization transcription analysis

Anoop Kumar Tiwari , Devansh Jain , Jayesh Kumar Tiwari , Shyam Kishore , Akhilesh Kumar Singh , Sushant Kumar Shrivastava , Arun Khattri
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Abstract

Oral cancer is a major public health concern around the globe, and its classification relies on factors such as habitual status and tumor stages. However, a significant gap exists in understanding oral cancer patients' molecular and genomic characteristics. This study aims to bridge this gap by analyzing International Cancer Genome Consortium (ICGC's) oral cancer data, which identified 2270 differentially expressed genes related to oral cancer. We employed pathway enrichment analysis, highlighting key pathways including hypoxia, VEGF, PI3K, and TGF-β, and STAT2, E2F4, and SP1 transcription factors enriched in tumor samples compared to normal samples. Moreover, we utilized a non-negative matrix factorization (NMF) technique for unsupervised subtype discovery and identified three distinct tumor subgroups. Each subgroup exhibited unique molecular profiles, with pathways related to TNF-α, NF-κB, and hypoxia enriched across all groups. Notably, transcription factor analysis revealed crucial differences: subgroup A was enriched in EGR1, TP53, and HIF1A; subgroup B showed high levels of CDX2 and HNF4A; while subgroup C was characterized by enrichment in ATF4 and E2F4. These findings suggest the feasibility of classifying oral squamous cell carcinoma (OSCC) patients based on gene expression profiles, laying a foundational framework for future research aimed at personalized treatment strategies.
解密口腔癌亚型:整合差异基因表达和通路分析,然后进行非负性基质因子化转录分析
口腔癌是全球主要的公共卫生问题,其分类依赖于习惯状态和肿瘤分期等因素。然而,在了解口腔癌患者的分子和基因组特征方面存在很大的差距。本研究旨在通过分析国际癌症基因组联盟(ICGC)的口腔癌数据来弥补这一差距,该数据确定了2270个与口腔癌相关的差异表达基因。我们采用途径富集分析,突出了肿瘤样本中与正常样本相比,缺氧、VEGF、PI3K、TGF-β以及STAT2、E2F4和SP1转录因子富集的关键途径。此外,我们利用非负矩阵分解(NMF)技术进行无监督亚型发现,并确定了三个不同的肿瘤亚组。每个亚组都表现出独特的分子特征,与TNF-α, NF-κB和缺氧相关的途径在所有组中都富集。值得注意的是,转录因子分析揭示了关键的差异:A亚组富含EGR1、TP53和HIF1A;B亚组CDX2和HNF4A水平较高;而C亚组以ATF4和E2F4富集为特征。本研究结果提示基于基因表达谱对口腔鳞状细胞癌(OSCC)患者进行分类的可行性,为未来针对个性化治疗策略的研究奠定基础框架。
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