<i>TERT</i> promoter mutation positive oral cavity carcinomas, a clinically and genetically distinct subgroup of head and neck squamous cell carcinomas

Saito, Yuki; Kage, Hidenori; Kobayashi, Kenya; Yoshida, Masafumi; Fukuoka, Osamu; Yamamura, Koji; Mukai, Toshiyuki; Oda, Katsutoshi; Yamasoba, Tatsuya

doi:10.1002/hed.27540

Cited by 2 publications

(2 citation statements)

References 25 publications

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“…Post-transcriptional regulation includes miRNA-mediated processes, where dysregulation of microRNAs targeting TERT may lead to increased mRNA stabilization and elevated TERT expression in OSCC. The complex interplay of these mechanisms underscores the diverse and signi cant role of TERT in OSCC development and progression [116,117].…”

Section: Role Of Tert In Oral Squamous Cell Carcinoma (Oscc)mentioning

confidence: 99%

Mutational Landscape of Oral Squamous Cell Carcinoma Investigated Through the Developmental Dynamics of Oral Squamous Epithelium

Shafi,

Aakash,

Haseeb

et al. 2024

Preprint

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Background: Oral Squamous Cell Carcinoma (OSCC) poses a global health challenge, demanding an in-depth understanding of its mutational landscape. The complex mutational profile underscores the need for targeted therapies. OSCC's impact on crucial functions necessitates precise interventions for improved patient outcomes. This investigation into OSCC's mutational landscape through developmental biology aims to fill critical knowledge gaps, contributing possibly towards future personalized therapies and advancing our approach to this challenging malignancy. Methods: Databases, including PubMed, MEDLINE, Google Scholar, and open access/subscription-based journals were searched for published articles without any date restrictions, to investigate the mutational landscape of OSCC through the lens of developmental dynamics. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate OSCC oncogenesis. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: This study into Oral Squamous Cell Carcinoma (OSCC) reveals a complex genetic landscape marked by mutations in key regulators including TP53, CASP8, CDKN2A, FAT1, PIK3CA, and RYR2. TP53 emerges as a central player, with mutations disrupting its tumor-suppressive functions and influencing developmental processes in OSCC. Dysregulated Notch1 signaling contributes to aberrant cell differentiation and tissue morphogenesis. JAK/STAT and SHH signaling, essential for normal oral epithelial development, exhibit dual dynamics in OSCC, influencing both normal developmental processes and tumorigenesis. Implications for precision medicine arise from the identified genetic alterations, offering potential targets for future therapeutic interventions. Notch1 and TP53 signaling pathways emerge as promising targets, while modulating JAK/STAT and SHH signaling presents challenges and opportunities for new therapeutic strategies. Conclusion: This study reveals genetic complexities and regulatory networks disrupted in OSCC carcinogenesis and also playing key roles in developmental dynamics of oral squamous epithelium. Key genes like TP53 and Notch1, integral to oral epithelial development, undergo dysregulation, influencing OSCC initiation. JAK/STAT and SHH signaling, crucial in normal development, exhibit dual roles, contributing to OSCC progression. This study also points to targeted therapeutic strategies that may emerge in future by investigating OSCC through developmental dynamics. Further research may provide deeper insights into the complex developmental biology, paving the way for enhanced interventions in OSCC.

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Section: Role Of Tert In Oral Squamous Cell Carcinoma (Oscc)mentioning

confidence: 99%

Mutational Landscape of Oral Squamous Cell Carcinoma Investigated Through the Developmental Dynamics of Oral Squamous Epithelium

Shafi,

Aakash,

Haseeb

et al. 2024

Preprint

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“… 7 Mutations or deletions within this gene have been linked to numerous cancers, establishing its significance as a critical oncogene. Recent literature 8 , 9 , 10 indicates that while apoptosis induction remains a common chemotherapeutic action mechanism, primary apoptosis regulators, notably p53 and p16/CDKN2A, are often inactivated within tumour tissues, which can lead to resistance against such treatments.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of CDKN2A in head and neck squamous cell carcinoma via pathomics and machine learning

Wang,

Zhou,

et al. 2024

J Cellular Molecular Medi

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This study aims to enhance the prognosis prediction of Head and Neck Squamous Cell Carcinoma (HNSCC) by employing artificial intelligence (AI) to analyse CDKN2A gene expression from pathology images, directly correlating with patient outcomes. Our approach introduces a novel AI‐driven pathomics framework, delineating a more precise relationship between CDKN2A expression and survival rates compared to previous studies. Utilizing 475 HNSCC cases from the TCGA database, we stratified patients into high‐risk and low‐risk groups based on CDKN2A expression thresholds. Through pathomics analysis of 271 cases with available slides, we extracted 465 distinctive features to construct a Gradient Boosting Machine (GBM) model. This model was then employed to compute Pathomics scores (PS), predicting CDKN2A expression levels with validation for accuracy and pathway association analysis. Our study demonstrates a significant correlation between higher CDKN2A expression and improved median overall survival (66.73 months for high expression vs. 42.97 months for low expression, p = 0.013), establishing CDKN2A's prognostic value. The pathomic model exhibited exceptional predictive accuracy (training AUC: 0.806; validation AUC: 0.710) and identified a strong link between higher Pathomics scores and cell cycle activation pathways. Validation through tissue microarray corroborated the predictive capacity of our model. Confirming CDKN2A as a crucial prognostic marker in HNSCC, this study advances the existing literature by implementing an AI‐driven pathomics analysis for gene expression evaluation. This innovative methodology offers a cost‐efficient and non‐invasive alternative to traditional diagnostic procedures, potentially revolutionizing personalized medicine in oncology.

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TERT promoter mutation positive oral cavity carcinomas, a clinically and genetically distinct subgroup of head and neck squamous cell carcinomas

Cited by 2 publications

References 25 publications

Mutational Landscape of Oral Squamous Cell Carcinoma Investigated Through the Developmental Dynamics of Oral Squamous Epithelium

Mutational Landscape of Oral Squamous Cell Carcinoma Investigated Through the Developmental Dynamics of Oral Squamous Epithelium

Prognostic value of CDKN2A in head and neck squamous cell carcinoma via pathomics and machine learning

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