Khan Mohammed Muzamil, Frustino Jennifer, Villa Alessandro, Nguyen Bach-Cuc, Woo Sook-Bin, Johnson William Evan, Varelas Xaralabos, Kukuruzinska Maria, Monti Stefano
Section of Computational Biomedicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
Bioinformatics Graduate Program, Boston University, Boston, MA, USA.
bioRxiv. 2023 Mar 24:2023.03.24.534064. doi: 10.1101/2023.03.24.534064.
Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and 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 towards 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.
Patients harboring oral premalignant lesions (PMLs) have an increased risk of developing oral squamous cell carcinoma (OSCC), but the underlying mechanisms driving transformation of PMLs to OSCC remain poorly understood. In this study, Khan et al., analyzed a newly generated dataset of gene expression and microbial profiles of oral tissues from patients diagnosed with PMLs from differing histopathological groups, including hyperkeratosis not reactive ( ) and dysplasia, comparing these profiles with OSCC and normal oral mucosa. Significant similarities between PMLs and OSCC were observed, with PMLs manifesting several cancer hallmarks, including oncogenic and immune pathways. The study also demonstrates associations between the abundance of multiple microbial species and PML groups, suggesting a potential contribution of the oral microbiome to the early stages of OSCC development. The study offers insights into the nature of the molecular, cellular and microbial heterogeneity of oral PMLs and suggests that molecular and clinical refinement of PMLs may provide opportunities for early disease detection and interception.
头颈癌是一种复杂的恶性肿瘤，包括多个解剖部位，口腔癌是全球最致命且最具毁容性的癌症之一。口腔癌（OC）是头颈癌病例的一个子集，主要表现为与烟草和酒精相关的口腔鳞状细胞癌（OSCC），其5年生存率约为65%，部分原因是缺乏早期检测和有效治疗方法。OSCC通过一系列多步骤的临床和组织病理学阶段，从口腔中的癌前病变（PMLs）发展而来，包括不同程度的上皮发育异常。为了深入了解与PMLs进展为OSCC相关的分子机制，我们分析了66例人类PMLs的全转录组，这些PMLs包括有发育异常的白斑和无反应性角化过度（HkNR）病变，同时设置了健康对照和OSCC样本。我们的数据显示，PMLs在与细胞可塑性相关的基因特征中富集，如部分上皮-间质转化（p-EMT）表型，以及与免疫反应相关的基因特征。对宿主转录组和微生物组的综合分析进一步突出了微生物丰度差异与PML途径活性之间的显著关联，表明口腔微生物群对PMLs向OSCC的演变有一定作用。总的来说，这项研究揭示了与PMLs进展相关的分子过程，这可能有助于早期诊断和疾病的早期干预。
患有口腔癌前病变（PMLs）的患者患口腔鳞状细胞癌（OSCC）的风险增加，但PMLs转化为OSCC的潜在机制仍知之甚少。在这项研究中，Khan等人分析了一个新生成的数据集，该数据集包含来自不同组织病理学组（包括无反应性角化过度和发育异常）的被诊断为PMLs的患者口腔组织的基因表达和微生物谱，并将这些谱与OSCC和正常口腔黏膜进行比较。观察到PMLs与OSCC之间有显著相似性，PMLs表现出多种癌症特征，包括致癌和免疫途径。该研究还证明了多种微生物物种的丰度与PML组之间的关联，表明口腔微生物群可能对OSCC发展的早期阶段有潜在作用。这项研究深入了解了口腔PMLs的分子、细胞和微生物异质性的本质，并表明对PMLs进行分子和临床细化可能为疾病的早期检测和干预提供机会。
