Mapping the Nordic Research Landscape for the period 2016-2020: a comprehensive study of research outcomes, collaborations, and impact.

Background: This article aims to study the research outcomes of five Nordic countries in terms of research publications, spend on R&D, outcomes and collaborations as these are important parameters to understand research thrust of the countries/regions, in addition to their innovation capability. Methods: The research outcomes of the Nordic countries in terms of the total number of publications, coauthored publications, publications with corporate collaborators, citations, the Field Weighted Citation Index (FWCI) and publications in different subject areas were retrieved using Scopus and its associate SciVal. The research outcomes were extracted for five years from 2016-2020. In addition, total population, researcher population and research spend of these countries have been obtained from World Bank data available for the year 2021. Results: The analysis showed that Sweden has the highest population and the highest number of researchers in this region. All countries have the highest number of coauthored publications with the United States, followed by the United Kingdom, except Iceland, which has the second highest number of coauthored publications with Sweden. Denmark, followed by Iceland, stands prominent with reference to having publications with corporate collaborations. Denmark and Sweden have a high percentage of articles in first quartile journals, which is above the average for Nordic countries. Iceland stands at the top with the highest citations, which is depicted by high FWCI. Across subject areas, the Nordic countries have maximum publications in life sciences. Other prominent subject areas include technology and natural sciences. Conclusion: On analysing the research landscape of Nordic countries, maximum research output is in the field of life sciences and medicine, and most of the coauthored publications of these countries are with the United States. Denmark, with its exemplary research output, excels with maximum papers in top quartile journals and with maximum corporate collaborations and the highest FWCI.

Nanoparticles in CNS Therapeutics: Pioneering Drug Delivery Advancements.

INTRODUCTION: The incidence of Central Nervous System (CNS) disorders, including Parkinson's disease, Alzheimer's disease, stroke, and malignancies, has risen significantly in recent decades, contributing to millions of deaths annually. Efficacious treatment of these disorders requires medicines targeting the brain. The Blood-Brain Barrier (BBB) poses a formidable challenge to effective drug delivery to the brain, hindering progress in CNS therapeutics. This review explores the latest developments in nanoparticulate carriers, highlighting their potential to overcome BBB limitations. OBJECTIVE: This study aimed to evaluate and summarise the critical factors and pathways in the nanoparticle- based central nervous system's targeted drug delivery. METHODS: An extensive literature search was conducted, comprising the initial development of nanoparticle- based central nervous system-targeted drug delivery approaches to the latest advancements using various online search tools. RESULTS: The properties of nanoparticles, such as type of nanoparticles, size, shape, surface charge, hydrophobicity, and surface functionalisation, along with properties of the blood-brain barrier during normal and pathological conditions and their impact on the delivery of nanoparticles across the BBB, are identified and discussed here. CONCLUSION: Important properties and pathways that determine the penetration of nanoparticles across the central nervous system are reviewed in this article, along with recent advances in the field.

Mapping oral medicine (stomatology) & oral and maxillofacial pathology international organizations: a scoping review of global data and historical analysis.

OBJECTIVES: To describe the historical evolution and dissemination of the Oral Medicine and Oral and Maxillofacial Pathology international societies and associations across the globe, and to provide insights into their significant contributions toward oral health promotion. STUDY DESIGN: This review was conducted in accordance with the JBI Scoping Review Methodology Group guidance. The reporting followed the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR). RESULTS: Search strategy was applied to 5 databases (MEDLINE/PubMed, Scopus, Embase, Web of Science, Latin American and Caribbean Health Sciences (LILACS)) and grey literature (Google Scholar, Open Grey and ProQuest), as well as additional sources, such as organization websites. Eighty-nine sources were included in this review. Forty-six professional associations/societies were identified, of which 39 represented a country or geopolitical region, 2 represented continents, 2 represented multinational organizations and 3 multinational study groups. CONCLUSIONS: Documentation of the historical establishment and development of Oral Medicine and Oral and Maxillofacial Pathology organizations worldwide is limited and describing these processes remains challenging. Analysis of global data reveals heterogeneous development and distribution, resulting in disparities in accessibility and standardization. Further efforts toward oral health promotion should be implemented.

Metastatic Intestinal Adenocarcinoma: A Rare Case Involving the Mandible.

BACKGROUND: Metastatic intestinal adenocarcinoma involving the mandible is rare, posing diagnostic challenges because of its unusual presentation. CASE PRESENTATION: A 55-year-old male presented with a rapidly growing mass in the right mandible, accompanied by facial asymmetry and vestibular obliteration. Histopathological examinations revealed features consistent with adenocarcinoma. Immunohistochemical analysis supported the diagnosis of intestinal adenocarcinoma, with subsequent metastasis confirmed by PET scan findings. DIAGNOSIS: The lesion was conclusively diagnosed as intestinal adenocarcinoma metastasizing to the mandible. MANAGEMENT: The patient pursued treatment at a government facility, leading to a loss of follow-up.

Pan-cancer exploration of oncogenic and clinical impacts revealed that HOXA9 is a diagnostic indicator of tumorigenesis.

Homeodomain transcription factor A9 (HOXA9) is a member of the HOX cluster family of transcription factors that are crucially involved in embryo implantation, morphogenesis, body axis development, and endothelial cell differentiation. Despite numerous reports on its aberrant expression in a few malignancies, the molecular and functional complexity of HOXA9 across cancers remains obscure. We aimed to analyze the dynamic role of HOXA9 across cancers by identifying, analyzing, and understanding its multiple modes of regulation and functional implications and identifying possible therapeutic avenues. We conducted a comprehensive analysis to determine the role of HOXA9 across cancers. This approach involved the integration of large-scale datasets from public repositories such as the Genomic Data Commons, specifically the Cancer Genome Atlas (GDC-TCGA), across 33 different cancer types. The multiple modes of HOXA9 regulation by genetic and epigenetic factors were determined using online tools, which comprised experimentally validated observations. Furthermore, downstream pathways were identified by predicting the targets of HOXA9 and by performing functional enrichment analysis. We also assessed the clinical significance of HOXA9 in terms of prognosis and stage stratification. This study evaluated the correlation between HOXA9 and tumor-infiltrating molecules and discussed its association with therapeutically approved antineoplastic drugs. HOXA9 was significantly upregulated in 9 tumors and downregulated in 2 cancers. The deregulation of HOXA9 is primarily attributed to epigenetic factors, including promoter DNA methylation and noncoding RNAs (ncRNAs). The HOXA9 transcription factor interacts with PBX/MEIS cofactors and regulates multiple genes involved in cancer-associated EMT, autophagy, the cell cycle, metabolic pathways, Wnt signaling, TGF-ß signaling, the AMPK pathway, PI3K/AKT signaling, and NF-κB signaling, thereby establishing control over downstream mechanisms. Differential expression in various clinical stages across cancers was shown to have prognostic significance and to be correlated with tumor-infiltrating immune molecules. The assessment of the correlation of HOXA9 expression with approved antineoplastic drugs revealed that targeting HOXA9 could be the most reliable strategy for preventing cancer progression. HOXA9 is upregulated in the majority of malignancies and drives cancer progression by regulating multiple signaling mechanisms. Hence, HOXA9 could be a reliable diagnostic indicator and a potential therapeutic candidate for solid cancer types.

Areca nut-induced oral fibrosis - Reassessing the biology of oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF) is a pathological condition characterized by excessive tissue healing resulting from physical, chemical, or mechanical trauma. Notably, areca nut consumption significantly contributes to the development of oral fibrosis. The current definition of OSF, recognizing its potential for malignant transformation, necessitates a more comprehensive understanding of its pathophysiology and etiology. HIGHLIGHTS: Areca nut induces fibrotic pathways by upregulating inflammatory cytokines such as TGF-ß and expressing additional cytokines. Moreover, it triggers the conversion of fibroblasts to myofibroblasts, characterized by α-SMA and γSMA expression, resulting in accelerated collagen production. Arecoline, a component of areca nut, has been shown to elevate levels of reactive oxygen species, upregulate the expression of various cytokines, and activate specific signaling pathways (MEK, COX2, PI3K), all contributing to fibrosis. Therefore, we propose redefining OSF as "Areca nut-induced oral fibrosis" (AIOF) to align with current epistemology, emphasizing its distinctive association with areca nut consumption. The refined definition enhances our ability to develop targeted interventions, thus contributing to more effective prevention and treatment strategies for oral submucous fibrosis worldwide. CONCLUSION: Arecoline plays a crucial role as a mediator in fibrosis development, contributing to extracellular matrix accumulation in OSF. The re-evaluation of OSF as AIOF offers a more accurate representation of the condition. This nuanced perspective is essential for distinguishing AIOF from other forms of oral fibrosis and advancing our understanding of the disease's pathophysiology.

The interplay of EMT and stemness driving malignant transformation of Oral Submucous Fibrosis.

Background: Oral submucous fibrosis (OSF) is a persistent oral mucosal condition that carries an elevated risk of undergoing malignant transformation. Our objective was to elucidate the involvement of epithelial-to-mesenchymal transition (EMT) in OSF and its progression to malignancy by studying a panel of EMT markers, thereby understanding the molecular mechanisms. Methods: An immunohistochemical analysis was done to detect the presence of E-cadherin, N-cadherin, pan-cytokeratin (PanCK), vimentin, α-SMA (alpha-smooth muscle actin), and CD44 in a total of 100 tissue samples. These samples comprised 40 cases of OSF, 20 cases of oral squamous cell carcinoma associated with OSF (OSFSCC), and 40 cases of oral squamous cell carcinoma (OSCC). A whole transcriptomic analysis was performed on a group of seven matched samples encompassing NOM, OSF, OSFSCC, and OSCC. Results: We observed significantly decreased expression of E-cadherin and PanCK, while N-cadherin, vimentin, α-SMA, and CD44 showed significantly higher expression in OSFSCC and OSCC as compared to OSF, both at protein and RNA levels. CD44 expression was noticeably higher in OSFSCC (p < 0.001) than in OSCC. Conclusion: Downregulation of epithelial markers with concomitant upregulation of mesenchymal and stem cell markers suggests the potential role of EMT and stemness in accelerating the pathogenesis and malignant transformation of OSF. The high levels of CD44 expression seen in OSFSCC indicate a high propensity for aggressiveness and acquisition of stem-like characteristics by the cells undergoing EMT.

Exploring the regulatory interactions between mutated genes and homeobox genes in the head and neck cancer progression.

OBJECTIVE: Understanding the regulatory role of homeobox (HOX) and mutated genes in the progression of head and neck cancers is essential, although their interaction remains elusive. This study aims to decipher the critical regulation of mutation driven effects on homeobox genes to enhance our understanding of head and neck cancer progression. METHODS: Genomic mutation data from The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma were analyzed using VarScan2 for somatic variant detection. Mutational clustering, driver mutation identification, and cancer signaling pathway analysis were performed using the OncodriveCLUST method. Harmonizome datasets were retrieved to identify critical cancer driver genes affecting HOX genes. The effects of HPV infection on HOX and mutated genes were assessed using the oncoviral database. Altered pathway activity due to the effects of cancer drivers on HOX genes was analyzed with Gene Set Cancer Analysis. Functional enrichment analysis of gene ontology biological processes and molecular functions was conducted using the ClusterProfiler R package. RESULTS: Significant alterations in HOX genes were observed in head and neck cancer cohorts with mutated TP53, FAT1, and CDKN2A. HOX genes were identified as functionally downstream targets of TP53, signifying transcriptionally mediated regulation. The interaction between HOX genes and mutated TP53, FAT1, and CDKN2A dysregulated the epithelial-to-mesenchymal transition, cell cycle, and apoptosis pathways in head and neck cancer progression. CONCLUSION: The interplay between cancer driver genes and HOX genes is pivotal in regulating the oncogenic processes underlying the pathogenesis of head and neck squamous cell carcinoma.

HOXA9 transcription factor is a double-edged sword: from development to cancer progression.

The HOXA9 transcription factor serves as a molecular orchestrator in cancer stemness, epithelial-mesenchymal transition (EMT), metastasis, and generation of the tumor microenvironment in hematological and solid malignancies. However, the multiple modes of regulation, multifaceted functions, and context-dependent interactions responsible for the dual role of HOXA9 as an oncogene or tumor suppressor in cancer remain obscure. Hence, unravelling its molecular complexities, binding partners, and interacting signaling molecules enables us to comprehend HOXA9-mediated transcriptional programs and molecular crosstalk. However, it is imperative to understand its central role in fundamental biological processes such as embryogenesis, foetus implantation, hematopoiesis, endothelial cell proliferation, and tissue homeostasis before designing targeted therapies. Indeed, it presents an enormous challenge for clinicians to selectively target its oncogenic functions or restore tumor-suppressive role without altering normal cellular functions. In addition to its implications in cancer, the present review also focuses on the clinical applications of HOXA9 in recurrence and drug resistance, which may provide a broader understanding beyond oncology, open new avenues for clinicians for accurate diagnoses, and develop personalized treatment strategies. Furthermore, we have also discussed the existing therapeutic options and accompanying challenges in HOXA9-targeted therapies in different cancer types.

A bibliometric analysis of publication output in selected South American countries.

Research output provides an insight into the development of the scientific capability of a country. Budget allocation for research and development (R&D) is directly proportional to the research output of a country. Bibliometric analysis of South American countries has not been done in many studies. The purpose of this paper was to analyse research outputs from South American countries on various metrics. An analysis was done for a period of 11 years from 2010 to 2020. The analysis revealed that Brazil with highest percentage of research spend has lowest Field Weighted Citation Impact (FWCI). This contrasts with Uruguay, whose FWCI is high despite comparatively lower spend on R&D and lower publication output. Although Argentina has the highest percentage of researchers per million population (1202), it has the least papers per researchers (0.3 per year) among the countries studied. A huge disparity in terms of percentage of research spent, research output, papers per researcher, and output with national and international co-authorship was observed.

Development of Automated Risk Stratification for Sporadic Odontogenic Keratocyst Whole Slide Images with an Attention-Based Image Sequence Analyzer.

(1) Background: The categorization of recurrent and non-recurrent odontogenic keratocyst is complex and challenging for both clinicians and pathologists. What sets this cyst apart is its aggressive nature and high likelihood of recurrence. Despite identifying various predictive clinical/radiological/histopathological parameters, clinicians still face difficulties in therapeutic management due to its inherent aggressive nature. This research aims to build a pipeline system that accurately detects recurring and non-recurring OKC. (2) Objective: To automate the risk stratification of OKCs as recurring or non-recurring based on whole slide images (WSIs) using an attention-based image sequence analyzer (ABISA). (3) Materials and methods: The presented architecture combines transformer-based self-attention mechanisms with sequential modeling using LSTM (long short-term memory) to predict the class label. This architecture leverages self-attention to capture spatial dependencies in image patches and LSTM to capture sequential dependencies across patches or frames, making it suitable for this image analysis. These two powerful combinations were integrated and applied on a custom dataset of 48 labeled WSIs (508 tiled images) generated from the highest zoom level WSI. (4) Results: The proposed ABISA algorithm attained 0.98, 1.0, and 0.98 testing accuracy, recall, and area under the curve, respectively, whereas VGG16, VGG19, and Inception V3, standard vision transformer attained testing accuracies of 0.80, 0.73, 0.82, 0.91, respectively. ABISA used 58% fewer trainable parameters than the standard vision transformer. (5) Conclusions: The proposed novel ABISA algorithm was integrated into a risk stratification pipeline to automate the detection of recurring OKC significantly faster, thus allowing the pathologist to define risk stratification faster.

Building Automation Pipeline for Diagnostic Classification of Sporadic Odontogenic Keratocysts and Non-Keratocysts Using Whole-Slide Images.

The microscopic diagnostic differentiation of odontogenic cysts from other cysts is intricate and may cause perplexity for both clinicians and pathologists. Of particular interest is the odontogenic keratocyst (OKC), a developmental cyst with unique histopathological and clinical characteristics. Nevertheless, what distinguishes this cyst is its aggressive nature and high tendency for recurrence. Clinicians encounter challenges in dealing with this frequently encountered jaw lesion, as there is no consensus on surgical treatment. Therefore, the accurate and early diagnosis of such cysts will benefit clinicians in terms of treatment management and spare subjects from the mental agony of suffering from aggressive OKCs, which impact their quality of life. The objective of this research is to develop an automated OKC diagnostic system that can function as a decision support tool for pathologists, whether they are working locally or remotely. This system will provide them with additional data and insights to enhance their decision-making abilities. This research aims to provide an automation pipeline to classify whole-slide images of OKCs and non-keratocysts (non-KCs: dentigerous and radicular cysts). OKC diagnosis and prognosis using the histopathological analysis of tissues using whole-slide images (WSIs) with a deep-learning approach is an emerging research area. WSIs have the unique advantage of magnifying tissues with high resolution without losing information. The contribution of this research is a novel, deep-learning-based, and efficient algorithm that reduces the trainable parameters and, in turn, the memory footprint. This is achieved using principal component analysis (PCA) and the ReliefF feature selection algorithm (ReliefF) in a convolutional neural network (CNN) named P-C-ReliefF. The proposed model reduces the trainable parameters compared to standard CNN, achieving 97% classification accuracy.

Nanotechnology-based mucoadhesive and mucus-penetrating drug-delivery systems for transbuccal drug delivery.

Buccal drug-delivery systems present a promising approach for the drug delivery to the buccal mucosa, addressing oral cavity-specific problems, enabling systemic delivery and minimizing adverse effects on biological systems. Numerous strategies have been proposed to load drug-containing nanoparticles (NPs) to the buccal mucosa for local and systemic applications. There has been considerable interest in the development of mucoadhesive buccal formulations, particularly hydrogel composites utilizing mucoadhesive films incorporating NPs. Drug permeability and controlled drug release through buccal drug delivery continues to pose a challenge despite the availability of various remedies. This review highlights the need for, mechanisms and latest advances in NP-based transbuccal drug delivery with a focus on various pathological disorders and examples and limitations of the different methods.

HOX cluster-embedded lncRNAs and epithelial-mesenchymal transition in cancer: Molecular mechanisms and therapeutic opportunities.

Although there has been substantial improvement in the treatment modalities, cancer remains the major cause of fatality worldwide. Metastasis, recurrence, and resistance to oncological therapies are the leading causes of cancer mortality. Epithelial-mesenchymal transition (EMT) is a complex biological process that allows cancer cells to undergo morphological transformation into a mesenchymal phenotype to acquire invasive potential. It encompasses reversible and dynamic ontogenesis by neoplastic cells during metastatic dissemination. Hence, understanding the molecular landscape of EMT is imperative to identify a reliable clinical biomarker to combat metastatic spread. Accumulating evidence reveals the role of HOX (homeobox) cluster-embedded long non-coding RNAs (lncRNAs) in EMT and cancer metastasis. They play a crucial role in the induction of EMT, modulating diverse biological targets. The present review emphasizes the involvement of HOX cluster-embedded lncRNAs in EMT as a molecular sponge, chromatin remodeler, signaling regulator, and immune system modulator. Furthermore, the molecular mechanisms behind therapy resistance and the potential use of novel drugs targeting HOX cluster-embedded lncRNAs in the clinical management of distant metastasis will be discussed.

Comprehensive analysis of microRNAs and their target genes in oral submucous fibrosis.

The objective of the study is to understand the role of experimentally validated microRNAs (miRNAs) contributing to the acquisition of oncogenic phenotype in oral submucous fibrosis (OSF) by computational analysis. A comprehensive review was carried out to corroborate and summarize altered miRNA expression in OSF by retrieving relevant publications querying MEDLINE, Web of Science, Embase, and Scopus. The association between the miRNA-mRNA was performed using miRTarBase 8.0. The visualization of the miRNA-mRNA interaction was plotted using Cytoscape. MIENTURNET was used for the pathway analysis. Enrichment analysis was carried out for elucidating the hierarchical functions of miRNAs related to the acquisition of biological processes involved in the development of cancer. Thirteen miRNAs (hsa-miR-499a, hsa-miR-200b, hsa-miR-200c, hsa-miR-1246, hsa-miR-31, hsa-miR-10b, hsa-miR-21, hsa-miR-203, hsa-miR-455, hsa-miR-760, hsa-miR-623, hsa-miR-610, and hsa-miR-509-3-5p) were found to be deregulated in OSF. A total of 371 experimentally validated genes were shown to be interacting with the OSF-associated miRNAs. The targets of antifibrotic and profibrotic miRNAs were enriched in the cancer-related pathways. Dysregulated miRNA and its target genes illustrate the physiological role of miRNAs in fibrosis. Understanding the miRNA-mediated fibrotic signaling and targetting the specific miRNA-target gene interaction might provide relevant cues to ameliorate the fibrotic disease.

Nanoparticle-mediated active and passive drug targeting in oral squamous cell carcinoma: current trends and advances.

Oral squamous cell carcinoma (OSCC) is an invasive and highly malignant cancer with significant morbidity and mortality. Existing treatments including surgery, chemotherapy and radiation have poor overall survival rates and prognosis. The intended therapeutic effects of chemotherapy are limited by drug resistance, systemic toxicity and adverse effects. This review explores advances in OSCC treatment, with a focus on lipid-based platforms (solid lipid nanoparticles, nanostructured lipid carriers, lipid-polymer hybrids, cubosomes), polymeric nanoparticles, self-assembling nucleoside nanoparticles, dendrimers, magnetic nanovectors, graphene oxide nanostructures, stimuli-responsive nanoparticles, gene therapy, folic acid receptor targeting, gastrin-releasing peptide receptor targeting, fibroblast activation protein targeting, urokinase-type plasminogen activator receptor targeting, biotin receptor targeting and transferrin receptor targeting. This review also highlights oncolytic viruses as OSCC therapy candidates.

Role of osteopontin in oral epithelial dysplasia, oral submucous fibrosis and oral squamous cell carcinoma.

Background: Inflammatory cells and cytokines in the chronically injured mucosa promote fibrosis in the oral submucous fibrosis (OSF) fibrotic milieu. Osteopontin (OPN) is a wound-healing mediator that upregulates the inflammatory response and is involved in the malignancy and fibrosis of multiple organ systems. Objectives: We investigated the expression of OPN in oral potentially malignant disorders (OPMDs) and oral squamous cell carcinomas (OSCCs) to determine its role in the malignant transformation and fibrosis of oral tissues. The expression of OPN in OPMDs and OSCCs was compared and correlated, and the role of OPN as a fibrotic mediator in OSF was explained. Study Design: A total of 30 cases of normal mucosa and OPMDs (mild dysplasia, severe dysplasia, OSF and OSCCs) were studied by purposive sampling. In these groups, OPN immunoreactivity was examined and correlated with clinical findings. Results: In mild dysplasia, OPN expression was restricted to the basal cell layer with moderate staining intensity. In severe dysplasia, it was extremely intense and extended throughout the epithelium. In the OSF, OPN expression was moderate in the perinuclear areas of the basal cell layer. The expression of OPN was very strong in OSCC. A flow diagram explaining the profibrotic role of OPN in OSF has been provided. Conclusion: A positive role of OPN in both pathogenesis and malignant transformation of OPMDs and OSCC has been demonstrated.

Salivary DNA methylation markers for cancer of oral cavity.

PURPOSE: Aberrant DNA methylation plays a crucial role in oral carcinogenesis. Our previous study demonstrated hypermethylation of DAPK1, LRPPRC, RAB6C, and ZNF471 promoters in patients with tongue squamous cell carcinoma compared with normal samples. Methylation profiling using salivary DNA is considered a non-invasive alternative to tissue samples. Hence, the present study tested the DNA methylation status of these four promoters as indicators of oral cancer progression. METHODS: We performed the bisulfite-based targeted next-generation sequencing of four candidate genes in saliva and tissue DNA from normal, premalignant, and squamous cell carcinoma subjects. The clinicopathological association, diagnostic, and prognostic utility of aberrant DNA methylation were evaluated using the TCGA-HNSCC dataset. Using the Xgboost algorithm and logistic regression, CpG sites were prioritized, and Receiver Operating Characteristic was generated. By Log-rank test and Kaplan-Meier (KM) curves, an association between methylation and overall survival (OS), disease-free interval (DFI), and progression-free interval (PFI) were computed. RESULTS: We identified all four genes as significantly hypermethylated in premalignant and malignant samples compared with normal samples. The methylation levels were comparable between saliva and tissue samples with an r-value of 0.6297 to 0.8023 and 0.7823 to 0.9419 between premalignant tissue vs. saliva and OC vs. saliva, respectively. We identified an inverse correlation between DAPK1, LRPPRC, RAB6C, and ZNF471 promoter methylation with their expression. A classifier of 8 differentially methylated CpG sites belonging to DAPK1, RAB6C, and ZNF471 promoters was constructed, showing an AUC of 0.984 to differentiate tumors from normal samples. The differential methylation status of DAPK1, LRPPRC, and ZNF71 promoters was prognostically important. Abnormal expression of all four genes was associated with immune infiltration. CONCLUSIONS: Thus, methylation analysis of these candidate CpG sites from saliva can be helpful as a non-invasive tool for the clinical management of OC.