Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre-malignant lesions and cancer

Abstract

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. Graphical abstract

About a Possible Impact of Endodontic Infections by Fusobacterium nucleatum or Porphyromonas gingivalis on Oral Carcinogenesis: A Literature Overview

“…In fact, evidence indicates that both P. gingivalis and F. nucleatum are endowed with tumorigenic activities which are likely to favor OSCC onset and/or progression [5]. Confirming this, the dysplastic and/or hyperplastic lesions that often precede OSCC development (oral pre-malignant diseases, OPMDs) [8] are densely populated by pathogenic bacteria, including F. nucleatum or P. gingivalis, and display a reduced number of saprophytic bacteria as compared with healthy oral mucosa [9,10]. In OSCCs, the presence of F. nucleatum and P. gingivalis becomes even more evident, and its intensity parallels the clinical progression of the disease, positively correlating with the tumor size and lymph node metastases [9,10].…”

The management of oral cancer – current standards and future perspectives. Review of the literature

“…These conditions include whitish (leukoplakia) and red patches (erythroplasia, erythroplakia), lichen planus and rhomboid tongue inflammation. Conditions directly leading to the development of malignancy include small-, mediumand high-grade squamous metaplasia or dysplasia and carcinoma in situ [27,[29][30]. SCC accounts for more than 90% of all OCs [31][32].…”

Mechanisms and Potential Clinical Implications of Oral Microbiome in Oral Squamous Cell Carcinoma

“…A meta-analysis found that HPV 16/18 was strongly associated with OLP and OLK [21]. In general, continuous microbial changes are observed throughout the development of OSCC [22]. However, further research is required to elucidate the relationship between microbes and the risk of malignant transformation [23].…”