头颈部肿瘤是一种复杂的恶性肿瘤，包含多个解剖部位，口腔癌是全球最致命和最毁容的癌症之一。口腔癌作为头颈部癌症的一部分，主要表现为与烟草和酒精相关的口腔鳞癌（OSCC），5年生存率约为65%，部分原因是缺乏早期发现和有效治疗方法。OSCC通过口腔内蓄势待发的癌前病变（PMLs）经历了一系列多步骤的临床和组织病理学阶段，包括不同程度的上皮非典型增生。为了了解PMLs向OSCC进展的分子机制，我们对66例人类PMLs（包括白斑合并非典型增生和皮层增厚非反应性（HkNR）病理）以及健康对照组和OSCC的全转录组进行了分析。我们的数据显示，PMLs富集了与细胞可塑性相关的基因特征，例如部分上皮间质转化（p-EMT）表型，以及免疫应答。宿主转录组和微生物组的综合分析进一步凸显了微生物丰度差异与PMLs途径活性之间的显著相关性，暗示了口腔微生物组对PML进化为OSCC的贡献。总而言之，本研究揭示了与PML进展相关的分子过程，可能有助于早期诊断和疾病拦截。© 2023，BioMed Central Ltd.，Springer Nature的一部分。

Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and the most disfiguring cancers globally. Oral cancer (OC) constitutes a subset of head and neck cancer cases, presenting primarily as tobacco- and alcohol-associated oral squamous cell carcinoma (OSCC), with a 5-year survival rate of ~ 65%, partly due to the lack of early detection and effective treatments. OSCC arises from premalignant lesions (PMLs) in the oral cavity through a multi-step series of clinical and histopathological stages, including varying degrees of epithelial dysplasia. To gain insights into the molecular mechanisms associated with the progression of PMLs to OSCC, we profiled the whole transcriptome of 66 human PMLs comprising leukoplakia with dysplasia and hyperkeratosis non-reactive (HkNR) pathologies, alongside healthy controls and OSCC. Our data revealed that PMLs were enriched in gene signatures associated with cellular plasticity, such as partial EMT (p-EMT) phenotypes, and with immune response. Integrated analyses of the host transcriptome and microbiome further highlighted a significant association between differential microbial abundance and PML pathway activity, suggesting a contribution of the oral microbiome toward PML evolution to OSCC. Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage.© 2023. BioMed Central Ltd., part of Springer Nature.