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Diagnostics
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Advances in Oral Pathology of Basic and Clinical Cancer Research
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Advances in Oral Pathology of Basic and Clinical Cancer Research

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 1289

Special Issue Editor

Dr. Jun-Ichi Tanuma

E-Mail Website
Guest Editor
Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan
Interests: oral squamous cell carcinoma; head and neck cancer; oral oncology; biomarkers; prognostic markers; oral epithelial dysplasia; oral cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue, titled "Advances in Oral Pathology of Basic and Clinical Cancer Research", will be a comprehensive resource that explores the latest developments in both fundamental and clinical research on oral cancer. It will cover a wide range of topics, including new insights into molecular pathology, the tumor microenvironment, immunotherapy, and epigenetics in oral cancer. It will also delve into innovative diagnostic techniques, AI-powered image analysis, and public health initiatives for cancer prevention. Highlighting advancements in early diagnosis, targeted therapies, and personalized medicine, this work will provide valuable guidance for improving patient quality of life and outcomes. Thus, this Special Issue will be an invaluable resource not only for researchers and clinicians who specialize in oral cancer but also for all healthcare professionals interested in expanding their knowledge of oral pathology.

Dr. Jun-Ichi Tanuma
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • oral cancer
  • molecular pathology
  • tumor microenvironment (TME)
  • immunotherapy
  • epigenetics
  • diagnosis
  • targeted therapy
  • personalized medicine
  • AI and image analysis

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

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Research

15 pages, 7925 KB  
Article
DNA Hypermethylation at the Invasive Front of Oral Squamous Cell Carcinoma Confers Poorly Differentiated Characteristics and Promotes Migration of Cancer Cells
by Li-Po Wang, Chien-Ya Li, Yu-Hsueh Wu, Meng-Yen Chen, Yi-Ping Hsieh, Tze-Ta Huang, Tse-Ming Hong and Yuh-Ling Chen
Diagnostics 2025, 15(19), 2477; https://doi.org/10.3390/diagnostics15192477 - 27 Sep 2025
Viewed by 440
Abstract
Background/Objectives: Oral squamous cell carcinoma (OSCC) is a common and aggressive oral cancer with high recurrence and mortality rates, largely due to late diagnosis and metastasis. Epigenetic regulation, particularly aberrant DNA methylation, plays a critical role in cancer progression. Altered methylation patterns disrupt [...] Read more.
Background/Objectives: Oral squamous cell carcinoma (OSCC) is a common and aggressive oral cancer with high recurrence and mortality rates, largely due to late diagnosis and metastasis. Epigenetic regulation, particularly aberrant DNA methylation, plays a critical role in cancer progression. Altered methylation patterns disrupt cancer-related gene regulation. Our previous study found that oral cancer patients exhibit increased synthesis of S-adenosyl-L-methionine, a key methyl donor for cytosine methylation. Therefore, the aim of this study was to explore the relationship between global DNA methylation and OSCC progression and to evaluate the impact of DNA methylation heterogeneity on oral cancer cells. Methods: Immunohistochemistry (IHC) and immunofluorescence (IF) staining were used to examine 5-methylcytosine (5-mC) expression in OSCC clinical specimens and oral cancer cells. The DNA methyltransferase inhibitor 5-Aza-dC was used to assess the effects of DNA methylation on cell function and gene expression. RNA sequencing was used to identify key differentially expressed genes affected by 5-Aza-dC treatment. Cell migration was assessed using a wound closure assay. Protein and gene expression were analyzed using Western blotting and quantitative PCR. Results: An inverse relationship was found between 5-mC levels and cancer differentiation—poorly differentiated OSCC exhibited higher 5-mC levels. Additionally, higher 5-mC staining was observed at the invasion front of oral cancer tissues. In OSCC cells, 5-mC content correlated with migration ability. Furthermore, conditioned medium from cancer-associated fibroblasts enhanced both methylation levels and migration of OSCC cells. Treatment with 5-Aza-dC significantly increased epithelial differentiation, reduced epithelial-to-mesenchymal transition and cell adhesion-related genes, and inhibited OSCC cell migration. Conclusions: The findings highlight the critical role of DNA hypermethylation in OSCC progression, particularly in regulating differentiation, migration, and EMT. The interplay between the tumor microenvironment and epigenetic modifications underscores the complexity of OSCC biology and opens avenues for innovative therapeutic strategies. Full article
(This article belongs to the Special Issue Advances in Oral Pathology of Basic and Clinical Cancer Research)
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14 pages, 1735 KB  
Article
Tumor-Infiltrating Lymphocytes Predict Extranodal Extension and Prognosis in Regionally Advanced Oral Cavity Cancer
by Mia Lorencin Bulic, Martin Jurlina, Danko Müller, Lada Lijovic, Matija Mamic and Ivica Luksic
Diagnostics 2025, 15(19), 2431; https://doi.org/10.3390/diagnostics15192431 - 24 Sep 2025
Viewed by 410
Abstract
Background/Objectives: Oral cavity squamous cell carcinoma (OCSCC) is an aggressive malignancy, often diagnosed at an advanced stage and with stagnant survival outcomes despite advances in surgical and oncologic management. Tumor-infiltrating lymphocytes (TILs) have been explored as potential prognostic markers in many solid tumors; [...] Read more.
Background/Objectives: Oral cavity squamous cell carcinoma (OCSCC) is an aggressive malignancy, often diagnosed at an advanced stage and with stagnant survival outcomes despite advances in surgical and oncologic management. Tumor-infiltrating lymphocytes (TILs) have been explored as potential prognostic markers in many solid tumors; however, their role in OCSCC remains under researched. This study aimed to assess the prognostic value of TILs in a cohort of patients with regionally advanced, p16-negative squamous cell carcinoma of all oral cavity subsites and to evaluate for any correlation of TILs and extranodal extension (ENE). Methods: A retrospective study was conducted on 103 consecutive patients treated with comprehensive surgical resection. TILs were quantified using the standardized method proposed by the International Immuno-Oncology Biomarkers Working Group. Statistical analyses evaluated associations with a comprehensive set of independent variables and survival endpoints. Results: High stromal infiltration at the invasive margin (>25%) was independently associated with significantly improved overall survival (HR 4.53, p = 0.005), disease-specific survival (HR 4.49, p = 0.008), and disease-free survival (HR 3.42, p = 0.025). Patients with ENE demonstrated lower TILs compared with ENE-negative patients (median 40% vs. 57.5%), a difference that reached statistical significance in both parametric and nonparametric testing (Welch’s t-test p = 0.032; Mann–Whitney U p = 0.030). Conclusions: TILs quantified by this standardized method are a reliable, independent prognostic biomarker in regionally advanced OCSCC of all subsites and are also associated with extranodal extension of regional metases. This study gives rationale for consideration of inclusion of TILS into future immunotherapeutic decision-making and further investigations of TIL-ENE association. Full article
(This article belongs to the Special Issue Advances in Oral Pathology of Basic and Clinical Cancer Research)
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