{"title":"Mesenchymal stem cells in the management of oral submucous fibrosis—An enigma to be solved","authors":"Suvarna Kizhakkoottu, Pratibha Ramani, Wanninayake Mudiyanselage Tilakaratne","doi":"10.1111/jop.13539","DOIUrl":"https://doi.org/10.1111/jop.13539","url":null,"abstract":"","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"49 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Constanza Marín-Márquez, Janine Kirby, Keith D. Hunter
Ameloblastoma (AM) is a benign, although aggressive, epithelial odontogenic tumour originating from tooth-forming tissues or remnants. Its aetiopathogenesis remains unclear; however, molecular analysis techniques have allowed researchers to progress in understanding its genetic basis. The high frequency of BRAF p.V600E as a main driver mutation in AM is well established; nevertheless, it is insufficient to explain its tumourigenesis. In this review, we aimed to integrate the current knowledge about the biology of AM and to describe the main genetic alterations reported, focusing on the findings of large-scale sequencing and gene expression profiling techniques. Current evidence shows that besides BRAF mutation and activation of the MAPK pathway, alterations in Hedgehog and Wnt/β-catenin pathway-related genes are also involved in AM pathogenesis. Recently, a tumour suppressor gene, KMT2D, has been reported as mutated by different research groups. The biological impact of these mutations in the pathogenesis of AM has yet to be elucidated. Further studies are needed to clarify the impact of these findings in the identification of novel biomarkers that could be useful for diagnosing, classifying, and molecular targeting this neoplasm.
牙齿母细胞瘤（Ameloblastoma，AM）是一种良性、侵袭性上皮性牙源性肿瘤，起源于牙齿形成组织或残余组织。其发病机制尚不清楚，但分子分析技术使研究人员在了解其遗传基础方面取得了进展。BRAF p.V600E作为AM的主要驱动基因突变，其发生率很高，这一点已得到公认；然而，这还不足以解释其肿瘤发生的原因。在这篇综述中，我们旨在整合目前有关 AM 生物学的知识，并描述已报道的主要基因改变，重点关注大规模测序和基因表达谱分析技术的发现。目前的证据表明，除了BRAF突变和MAPK通路的激活外，Hedgehog和Wnt/β-catenin通路相关基因的改变也参与了AM的发病机制。最近，不同研究小组报告了一种肿瘤抑制基因 KMT2D 的突变。这些基因突变对AM发病机制的生物学影响尚待阐明。还需要进一步的研究来阐明这些发现对鉴定新型生物标志物的影响，这些生物标志物可能有助于诊断、分类和分子靶向治疗这种肿瘤。
{"title":"Molecular pathogenesis of ameloblastoma","authors":"Constanza Marín-Márquez, Janine Kirby, Keith D. Hunter","doi":"10.1111/jop.13538","DOIUrl":"10.1111/jop.13538","url":null,"abstract":"<p>Ameloblastoma (AM) is a benign, although aggressive, epithelial odontogenic tumour originating from tooth-forming tissues or remnants. Its aetiopathogenesis remains unclear; however, molecular analysis techniques have allowed researchers to progress in understanding its genetic basis. The high frequency of BRAF p.V600E as a main driver mutation in AM is well established; nevertheless, it is insufficient to explain its tumourigenesis. In this review, we aimed to integrate the current knowledge about the biology of AM and to describe the main genetic alterations reported, focusing on the findings of large-scale sequencing and gene expression profiling techniques. Current evidence shows that besides <i>BRAF</i> mutation and activation of the MAPK pathway, alterations in Hedgehog and Wnt/β-catenin pathway-related genes are also involved in AM pathogenesis. Recently, a tumour suppressor gene, <i>KMT2D</i>, has been reported as mutated by different research groups. The biological impact of these mutations in the pathogenesis of AM has yet to be elucidated. Further studies are needed to clarify the impact of these findings in the identification of novel biomarkers that could be useful for diagnosing, classifying, and molecular targeting this neoplasm.</p>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 5","pages":"277-293"},"PeriodicalIF":3.3,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Basal differentiation in oral squamous cell carcinoma is usually detected at invasive sites. However, its significance as a prognostic value has been poorly investigated.
Methods
COL17 was selected as a basal differentiation marker because of its stable expression in the basal-like cells of oral squamous cell carcinoma. Sixty-five cases of oral squamous cell carcinoma were subclassified into COL17-high (30 cases) and -low (35 cases) types, and the prognostic value was analyzed by Cox regression analysis. In addition, the stem cell markers such as SOX2, KLF4, MYC as well as the stem cell-related markers BMI1, EZH2, and YAP and its paralog TAZ, were immunohistochemically analyzed. Their prognostic values were investigated along with their COL17 status by Cox regression analysis.
Results
No significant difference was observed between the COL17-high and -low groups in the disease-specific survival and recurrence-free survival in oral squamous cell carcinoma. When the COL17-high and -low categories were combined with the SOX2, KLF4, EZH2, or YAP/TAZ status in the basal layers, together with gender and age as covariates, the hazard ratios reached 3.3, 3.7, 2.8, and 3.1, respectively. In addition, multivariate analysis, including COL17, SOX2, and KLF4, with gender and age as covariates, showed a significantly poor prognosis for disease-specific survival.
Conclusion
Based on the relatively high hazard ratios, it is indicated that basal differentiation and the expression status of SOX2 and KLF4 in the basal layers are prognostic factors for oral squamous cell carcinoma.
{"title":"Basal differentiation and expression status of SOX2 and KLF4 in basal layers are prognostic factors for disease-specific survival in oral squamous cell carcinoma","authors":"Kazuhiro Murakami, Tomoko Kamiakito, Hirotoshi Kawata, Koki Kosami, Takeo Nakaya, Tadahide Noguchi, Yoshiyuki Mori, Akira Tanaka","doi":"10.1111/jop.13535","DOIUrl":"10.1111/jop.13535","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Basal differentiation in oral squamous cell carcinoma is usually detected at invasive sites. However, its significance as a prognostic value has been poorly investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>COL17 was selected as a basal differentiation marker because of its stable expression in the basal-like cells of oral squamous cell carcinoma. Sixty-five cases of oral squamous cell carcinoma were subclassified into COL17-high (30 cases) and -low (35 cases) types, and the prognostic value was analyzed by Cox regression analysis. In addition, the stem cell markers such as SOX2, KLF4, MYC as well as the stem cell-related markers BMI1, EZH2, and YAP and its paralog TAZ, were immunohistochemically analyzed. Their prognostic values were investigated along with their COL17 status by Cox regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant difference was observed between the COL17-high and -low groups in the disease-specific survival and recurrence-free survival in oral squamous cell carcinoma. When the COL17-high and -low categories were combined with the SOX2, KLF4, EZH2, or YAP/TAZ status in the basal layers, together with gender and age as covariates, the hazard ratios reached 3.3, 3.7, 2.8, and 3.1, respectively. In addition, multivariate analysis, including COL17, SOX2, and KLF4, with gender and age as covariates, showed a significantly poor prognosis for disease-specific survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Based on the relatively high hazard ratios, it is indicated that basal differentiation and the expression status of SOX2 and KLF4 in the basal layers are prognostic factors for oral squamous cell carcinoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 5","pages":"303-309"},"PeriodicalIF":3.3,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Early diagnosis in oral cancer is essential to reduce both morbidity and mortality. This study explores the use of uncertainty estimation in deep learning for early oral cancer diagnosis.
Methods
We develop a Bayesian deep learning model termed ‘Probabilistic HRNet’, which utilizes the ensemble MC dropout method on HRNet. Additionally, two oral lesion datasets with distinct distributions are created. We conduct a retrospective study to assess the predictive performance and uncertainty of Probabilistic HRNet across these datasets.
Results
Probabilistic HRNet performs optimally on the In-domain test set, achieving an F1 score of 95.3% and an AUC of 96.9% by excluding the top 30% high-uncertainty samples. For evaluations on the Domain-shift test set, the results show an F1 score of 64.9% and an AUC of 80.3%. After excluding 30% of the high-uncertainty samples, these metrics improve to an F1 score of 74.4% and an AUC of 85.6%.
Conclusion
Redirecting samples with high uncertainty to experts for subsequent diagnosis significantly decreases the rates of misdiagnosis, which highlights that uncertainty estimation is vital to ensure safe decision making for computer-aided early oral cancer diagnosis.
{"title":"Deep neural network uncertainty estimation for early oral cancer diagnosis","authors":"Huiping Lin, Hanshen Chen, Jun Lin","doi":"10.1111/jop.13536","DOIUrl":"10.1111/jop.13536","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Early diagnosis in oral cancer is essential to reduce both morbidity and mortality. This study explores the use of uncertainty estimation in deep learning for early oral cancer diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We develop a Bayesian deep learning model termed ‘Probabilistic HRNet’, which utilizes the ensemble MC dropout method on HRNet. Additionally, two oral lesion datasets with distinct distributions are created. We conduct a retrospective study to assess the predictive performance and uncertainty of Probabilistic HRNet across these datasets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Probabilistic HRNet performs optimally on the In-domain test set, achieving an F1 score of 95.3% and an AUC of 96.9% by excluding the top 30% high-uncertainty samples. For evaluations on the Domain-shift test set, the results show an F1 score of 64.9% and an AUC of 80.3%. After excluding 30% of the high-uncertainty samples, these metrics improve to an F1 score of 74.4% and an AUC of 85.6%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Redirecting samples with high uncertainty to experts for subsequent diagnosis significantly decreases the rates of misdiagnosis, which highlights that uncertainty estimation is vital to ensure safe decision making for computer-aided early oral cancer diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 5","pages":"294-302"},"PeriodicalIF":3.3,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lin Chen, Yinyu Chen, Liangyu Ge, Qian Zhang, Jian Meng
Background
The differences between existing preclinical models and the tumor microenvironment in vivo are one of the significant challenges hindering cancer therapy development. Patient-derived tumor organoids (PDTO) can highly retain tumor heterogeneity. Thus, it provides a more reliable platform for research in tumor biology, new drug screening, and precision medicine.
Methods
We conducted a systematic review to summarise the characteristics of the existing preclinical models, the advantages of patient-derived tumor organoids in reconstructing the tumor microenvironment, and the latest research progress. Moreover, this study deciphers organoid culture technology in the clinical precision treatment of head and neck cancer to achieve better transformation. Studies were identified through a comprehensive search of Ovid MEDLINE (Wolters Kluwer), PubMed (National Library of Medicine), web of Science (Thomson Reuters) and, Scopus (Elsevier) databases, without publication date or language restrictions.
Results
In tumor development, the interaction between cellular and non-cellular components in the tumor microenvironment (TME) has a crucial role. Co-culture, Air-liquid interface culture, microfluidics, and decellularized matrix have depicted great potential in reconstructing the tumor microenvironment and simulating tumor genesis, development, and metastasis.
Conclusion
An accurate determination of stromal cells, immune cells, and extracellular matrix can be achieved by reconstructing the head and neck cancer tumor microenvironment using the PDTO model. Moreover, the interaction between head and neck cancer cells can also play an essential role in implementing the individualized precision treatment of head and neck cancer.
背景：现有临床前模型与体内肿瘤微环境之间的差异是阻碍癌症疗法开发的重大挑战之一。患者衍生肿瘤器官组织（PDTO）能高度保留肿瘤的异质性。因此，它为肿瘤生物学研究、新药筛选和精准医疗提供了更可靠的平台：我们进行了一项系统性综述，总结了现有临床前模型的特点、患者来源肿瘤器官组织在重建肿瘤微环境方面的优势以及最新的研究进展。此外，本研究还解读了类器官培养技术在头颈癌临床精准治疗中的应用，以实现更好的转化。这些研究是通过对 Ovid MEDLINE (Wolters Kluwer)、PubMed (National Library of Medicine)、web of Science (Thomson Reuters) 和 Scopus (Elsevier) 数据库的全面检索而确定的，没有出版日期或语言限制：在肿瘤发生发展过程中，肿瘤微环境（TME）中细胞和非细胞成分之间的相互作用起着至关重要的作用。共培养、气液界面培养、微流控和脱细胞基质在重建肿瘤微环境和模拟肿瘤发生、发展和转移方面具有巨大潜力：结论：使用 PDTO 模型重建头颈癌肿瘤微环境，可以准确测定基质细胞、免疫细胞和细胞外基质。此外，头颈部癌细胞之间的相互作用也对头颈部癌的个体化精准治疗起到至关重要的作用。
{"title":"Recent advances in patient-derived tumor organoids for reconstructing TME of head and neck cancer","authors":"Lin Chen, Yinyu Chen, Liangyu Ge, Qian Zhang, Jian Meng","doi":"10.1111/jop.13532","DOIUrl":"10.1111/jop.13532","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The differences between existing preclinical models and the tumor microenvironment in vivo are one of the significant challenges hindering cancer therapy development. Patient-derived tumor organoids (PDTO) can highly retain tumor heterogeneity. Thus, it provides a more reliable platform for research in tumor biology, new drug screening, and precision medicine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a systematic review to summarise the characteristics of the existing preclinical models, the advantages of patient-derived tumor organoids in reconstructing the tumor microenvironment, and the latest research progress. Moreover, this study deciphers organoid culture technology in the clinical precision treatment of head and neck cancer to achieve better transformation. Studies were identified through a comprehensive search of Ovid MEDLINE (Wolters Kluwer), PubMed (National Library of Medicine), web of Science (Thomson Reuters) and, Scopus (Elsevier) databases, without publication date or language restrictions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In tumor development, the interaction between cellular and non-cellular components in the tumor microenvironment (TME) has a crucial role. Co-culture, Air-liquid interface culture, microfluidics, and decellularized matrix have depicted great potential in reconstructing the tumor microenvironment and simulating tumor genesis, development, and metastasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>An accurate determination of stromal cells, immune cells, and extracellular matrix can be achieved by reconstructing the head and neck cancer tumor microenvironment using the PDTO model. Moreover, the interaction between head and neck cancer cells can also play an essential role in implementing the individualized precision treatment of head and neck cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 4","pages":"238-245"},"PeriodicalIF":3.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inhibin A and N6-methyladenosine methylation modifications participate in oral squamous cell carcinoma development. However, the N6-methyladenosine modification of Inhibin A in oral squamous cell carcinoma has not been revealed. This study reveals a key gene “Inhibin A” that may affect the tumorigenesis of oral squamous cell carcinoma and its molecular mechanisms on N6-methyladenosine methyltransferase KIAA1429-mediated N6-methyladenosine methylation modification.
Methods
Bioinformatics analysis and quantitative real-time polymerase chain reaction identified the potential regulatory genes in oral squamous cell carcinoma. We examined the changes in the proliferation (Cell Counting Kit-8 assay), migration (transwell migration assay), and invasion (transwell invasion assays) of oral squamous cell carcinoma cells. We performed a xenograft tumor experiment to validate the role of Inhibin A in oral squamous cell carcinoma in vivo. The interactions between Inhibin A and KIAA1429 were analyzed using bioinformatics, methylated RNA immunoprecipitation-qPCR, quantitative real-time polymerase chain reaction, and Western blotting experiments.
Results
Inhibin A had the highest expression in patients with oral squamous cell carcinoma. Inhibin A silencing impaired the ability of oral squamous cell carcinoma cells to proliferate, migrate, and invade, as well as limited the tumorous growth of oral squamous cell carcinoma cells in vivo. Bioinformatics analysis showed that Inhibin A expression positively interacted with KIAA1429 expression in The Cancer Genome Atlas database. The levels were also upregulated in our clinical samples. Furthermore, KIAA1429 silencing repressed the N6-methyladenosine level of Inhibin A in oral squamous cell carcinoma.
Conclusions
Inhibin A promotes the tumorigenesis of oral squamous cell carcinoma by KIAA1429-mediated N6-methyladenosine modification. This study adds to our current knowledge of the molecular mechanisms underlying oral squamous cell carcinoma malignancy.
背景：抑制素 A 和 N6-甲基腺苷甲基化修饰参与了口腔鳞状细胞癌的发展。然而，Inhibin A 在口腔鳞状细胞癌中的 N6-甲基腺苷修饰尚未被揭示。本研究揭示了可能影响口腔鳞状细胞癌肿瘤发生的关键基因 "Inhibin A "及其在N6-甲基腺苷甲基转移酶KIAA1429介导的N6-甲基腺苷甲基化修饰的分子机制：生物信息学分析和定量实时聚合酶链反应确定了口腔鳞状细胞癌的潜在调控基因。我们检测了口腔鳞状细胞癌细胞的增殖（细胞计数试剂盒-8检测法）、迁移（经孔迁移检测法）和侵袭（经孔侵袭检测法）的变化。我们进行了异种移植肿瘤实验，以验证 Inhibin A 在体内口腔鳞状细胞癌中的作用。我们利用生物信息学、甲基化 RNA 免疫沉淀-qPCR、定量实时聚合酶链反应和 Western 印迹实验分析了 Inhibin A 与 KIAA1429 之间的相互作用：结果：抑制素 A 在口腔鳞状细胞癌患者中的表达量最高。结果表明：Inhibin A在口腔鳞状细胞癌患者中的表达量最高，沉默Inhibin A可抑制口腔鳞状细胞癌细胞的增殖、迁移和侵袭能力，并限制口腔鳞状细胞癌细胞在体内的肿瘤生长。生物信息学分析表明，在癌症基因组图谱数据库中，Inhibin A的表达与KIAA1429的表达呈正相关。在我们的临床样本中，其水平也出现了上调。此外，KIAA1429沉默抑制了口腔鳞状细胞癌中Inhibin A的N6-甲基腺苷水平：结论：抑制素 A 通过 KIAA1429 介导的 N6-甲基腺苷修饰促进口腔鳞状细胞癌的肿瘤发生。这项研究丰富了我们目前对口腔鳞状细胞癌恶性肿瘤分子机制的认识。
{"title":"Inhibin A contributes to the tumorigenesis of oral squamous cell carcinoma by KIAA1429-mediated m6A modification","authors":"Xiaoqing Chen, Renxiu Fan","doi":"10.1111/jop.13531","DOIUrl":"10.1111/jop.13531","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inhibin A and N6-methyladenosine methylation modifications participate in oral squamous cell carcinoma development. However, the N6-methyladenosine modification of Inhibin A in oral squamous cell carcinoma has not been revealed. This study reveals a key gene “Inhibin A” that may affect the tumorigenesis of oral squamous cell carcinoma and its molecular mechanisms on N6-methyladenosine methyltransferase KIAA1429-mediated N6-methyladenosine methylation modification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Bioinformatics analysis and quantitative real-time polymerase chain reaction identified the potential regulatory genes in oral squamous cell carcinoma. We examined the changes in the proliferation (Cell Counting Kit-8 assay), migration (transwell migration assay), and invasion (transwell invasion assays) of oral squamous cell carcinoma cells. We performed a xenograft tumor experiment to validate the role of Inhibin A in oral squamous cell carcinoma in vivo. The interactions between Inhibin A and KIAA1429 were analyzed using bioinformatics, methylated RNA immunoprecipitation-qPCR, quantitative real-time polymerase chain reaction, and Western blotting experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Inhibin A had the highest expression in patients with oral squamous cell carcinoma. Inhibin A silencing impaired the ability of oral squamous cell carcinoma cells to proliferate, migrate, and invade, as well as limited the tumorous growth of oral squamous cell carcinoma cells in vivo. Bioinformatics analysis showed that Inhibin A expression positively interacted with KIAA1429 expression in The Cancer Genome Atlas database. The levels were also upregulated in our clinical samples. Furthermore, KIAA1429 silencing repressed the N6-methyladenosine level of Inhibin A in oral squamous cell carcinoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Inhibin A promotes the tumorigenesis of oral squamous cell carcinoma by KIAA1429-mediated N6-methyladenosine modification. This study adds to our current knowledge of the molecular mechanisms underlying oral squamous cell carcinoma malignancy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 4","pages":"266-274"},"PeriodicalIF":3.3,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luccas Lavareze, Talita de Carvalho Kimura, Erika Said Abu Egal, Albina Altemani, Fernanda Viviane Mariano
{"title":"Insights into morphological tissue changes induced by radiation therapy in head and neck cancer: Navigating diagnostic challenges","authors":"Luccas Lavareze, Talita de Carvalho Kimura, Erika Said Abu Egal, Albina Altemani, Fernanda Viviane Mariano","doi":"10.1111/jop.13530","DOIUrl":"10.1111/jop.13530","url":null,"abstract":"","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 4","pages":"236-237"},"PeriodicalIF":3.3,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rebeca Barros do Nascimento, Paloma Souza Gonçalves Cerqueira, Jamerson Carvalho Silva, Elisa Kauark Fontes, Elias Almeida dos Santos, Jean Nunes dos Santos, Fábio Daumas Nunes, Maria Fernanda Setubal Destro Rodrigues, Katiúcia Batista Silva Paiva, Flávia Caló de Aquino Xavier
Background
Cholesterol in cell membranes is crucial for cell signaling, adhesion, and migration. Membranes feature cholesterol-rich caveolae with caveolin proteins, playing roles in epithelial-mesenchymal transition and cancer progression. Despite elevated cholesterol levels in tumors, its precise function and the effects of its depletion in oral squamous cell carcinoma remain unclear. The aim of this study was to evaluate the influence of cholesterol depletion in oral squamous cell carcinoma cell line and epithelial-mesenchymal transition process.
Methods
Cholesterol depletion was induced on SCC-9 cells by methyl-β-cyclodextrin and cell viability, proliferation, apoptosis, and colony formation capacities were evaluated. Gene and protein expressions were evaluated by reverse transcription polymerase chain reaction (RT-qPCR) and Western Blot, respectively, and cell sublocalization was assessed by immunofluorescence.
Results
Cholesterol depletion resulted in alteration of oral squamous cell carcinoma cell morphology at different concentrations of methyl-β-cyclodextrin, as well as decreased cell proliferation and viability rates. Analysis of CAV1 transcript expression revealed increased gene expression in the treated SCC-9 during the 24 h period, at different concentrations of methyl-β-cyclodextrin: 5 , 7.5, 10, and 15 mM, in relation to parental SCC-9. CAV1 protein expression was increased, with subsequent dose-dependent decrease. A statistically significant difference was observed in samples treated with 5 mM of methyl-β-cyclodextrin (p = 0.02, Kruskal–Wallis test). The immunofluorescence assay showed lower cytoplasmic and membrane labeling intensity in the treated samples for CAV1.
Conclusion
These findings indicate the modulation of cholesterol as a possible mechanism underlying the regulation of these molecules and activation of epithelial-mesenchymal transition in oral squamous cell carcinoma.
背景：细胞膜中的胆固醇对细胞信号传导、粘附和迁移至关重要。细胞膜具有富含胆固醇的洞穴，内含洞穴素蛋白，在上皮-间质转化和癌症进展中发挥作用。尽管肿瘤中胆固醇水平升高，但其在口腔鳞状细胞癌中的确切功能及其耗竭的影响仍不清楚。本研究旨在评估胆固醇耗竭对口腔鳞状细胞癌细胞系及上皮-间质转化过程的影响：方法：用甲基-β-环糊精诱导SCC-9细胞去胆固醇，评估细胞活力、增殖、凋亡和集落形成能力。基因和蛋白质表达分别通过反转录聚合酶链反应（RT-qPCR）和 Western Blot 进行评估，细胞亚定位通过免疫荧光进行评估：结果：在不同浓度的甲基-β-环糊精中，胆固醇耗竭导致口腔鳞状细胞癌细胞形态改变，细胞增殖率和存活率降低。对 CAV1 转录物表达的分析表明，在不同浓度的甲基-β-环糊精（5、7.5、10 和 15 mM）条件下，经过处理的 SCC-9 细胞在 24 小时内的基因表达量比亲本 SCC-9 增加。CAV1 蛋白表达增加，随后随剂量减少。在使用 5 mM 甲基-β-环糊精处理的样本中观察到的差异具有统计学意义（P = 0.02，Kruskal-Wallis 检验）。免疫荧光检测显示，处理过的样本中 CAV1 的细胞质和膜标记强度较低：这些研究结果表明，胆固醇的调节是口腔鳞状细胞癌中这些分子的调控和上皮-间质转化激活的可能机制。
{"title":"Cholesterol depletion induces mesenchymal properties in oral squamous cell carcinoma cell line","authors":"Rebeca Barros do Nascimento, Paloma Souza Gonçalves Cerqueira, Jamerson Carvalho Silva, Elisa Kauark Fontes, Elias Almeida dos Santos, Jean Nunes dos Santos, Fábio Daumas Nunes, Maria Fernanda Setubal Destro Rodrigues, Katiúcia Batista Silva Paiva, Flávia Caló de Aquino Xavier","doi":"10.1111/jop.13524","DOIUrl":"10.1111/jop.13524","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cholesterol in cell membranes is crucial for cell signaling, adhesion, and migration. Membranes feature cholesterol-rich caveolae with caveolin proteins, playing roles in epithelial-mesenchymal transition and cancer progression. Despite elevated cholesterol levels in tumors, its precise function and the effects of its depletion in oral squamous cell carcinoma remain unclear. The aim of this study was to evaluate the influence of cholesterol depletion in oral squamous cell carcinoma cell line and epithelial-mesenchymal transition process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cholesterol depletion was induced on SCC-9 cells by methyl-β-cyclodextrin and cell viability, proliferation, apoptosis, and colony formation capacities were evaluated. Gene and protein expressions were evaluated by reverse transcription polymerase chain reaction (RT-qPCR) and Western Blot, respectively, and cell sublocalization was assessed by immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cholesterol depletion resulted in alteration of oral squamous cell carcinoma cell morphology at different concentrations of methyl-β-cyclodextrin, as well as decreased cell proliferation and viability rates. Analysis of CAV1 transcript expression revealed increased gene expression in the treated SCC-9 during the 24 h period, at different concentrations of methyl-β-cyclodextrin: 5 , 7.5, 10, and 15 mM, in relation to parental SCC-9. CAV1 protein expression was increased, with subsequent dose-dependent decrease. A statistically significant difference was observed in samples treated with 5 mM of methyl-β-cyclodextrin (<i>p</i> = 0.02, Kruskal–Wallis test). The immunofluorescence assay showed lower cytoplasmic and membrane labeling intensity in the treated samples for CAV1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings indicate the modulation of cholesterol as a possible mechanism underlying the regulation of these molecules and activation of epithelial-mesenchymal transition in oral squamous cell carcinoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 4","pages":"246-257"},"PeriodicalIF":3.3,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allan Vinícius Martins-de-Barros, Fábio Andrey da Costa Araújo, Ana Maria Ipólito Barros, Elenisa Glaucia Ferreira dos Santos, Adauto Gomes Barbosa Neto, Helker Albuquerque Macedo da Silva, Elker Lene Santos de Lima, Maria Tereza Cartaxo Muniz, Riedel Frota Sá Nogueira Neves, Rômulo Oliveira de Hollanda Valente, Emanuel Dias de Oliveira e Silva, Marianne de Vasconcelos Carvalho
Background
The objective of this study is to evaluate the diagnostic accuracy of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma.
Methods
This is a prospective diagnostic accuracy study conducted based on the Standards for Reporting Diagnostic Accuracy recommendations. The index test was the plasma-based liquid biopsy, whereas the reference standard was the conventional tissue biopsy. The target condition was the detection of BRAF V600E mutation. The study population consisted of individuals with ameloblastoma recruited from three tertiary hospitals from Brazil. A negative control group composed of three individuals with confirmed wild-type BRAF lesions were included. The participants underwent plasma circulating cell-free DNA and tumor tissue DNA isolation, and both were submitted to using competitive allele-specific TaqMan™ real-time polymerase chain reaction technology mutation detection assays. Sensitivity and specificity measures and positive and negative predictive values were calculated.
Results
Twelve patients with conventional ameloblastoma were included. BRAF V600E mutation was detected in 11/12 (91.66%) ameloblastoma tissue samples. However, the mutation was not detected in any of the plasma-based liquid biopsy circulating cell-free DNA samples in both ameloblastomas and negative control group. The sensitivity and specificity of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA was 0.0 and 1.0, respectively. The agreement between index test and reference standard results was 26.66%.
Conclusion
Plasma-based liquid biopsy does not seem to be an accurate method for the detection of the BRAF V600E mutation in circulating circulating cell-free DNA from patients with ameloblastoma, regardless of tumor size, anatomic location, recurrence status, and other clinicopathological features.
{"title":"It was not possible to detect BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma: A diagnostic accuracy study","authors":"Allan Vinícius Martins-de-Barros, Fábio Andrey da Costa Araújo, Ana Maria Ipólito Barros, Elenisa Glaucia Ferreira dos Santos, Adauto Gomes Barbosa Neto, Helker Albuquerque Macedo da Silva, Elker Lene Santos de Lima, Maria Tereza Cartaxo Muniz, Riedel Frota Sá Nogueira Neves, Rômulo Oliveira de Hollanda Valente, Emanuel Dias de Oliveira e Silva, Marianne de Vasconcelos Carvalho","doi":"10.1111/jop.13529","DOIUrl":"10.1111/jop.13529","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The objective of this study is to evaluate the diagnostic accuracy of plasma-based liquid biopsy for the detection of the <i>BRAF V600E</i> mutation in circulating cell-free DNA from patients with ameloblastoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a prospective diagnostic accuracy study conducted based on the Standards for Reporting Diagnostic Accuracy recommendations. The index test was the plasma-based liquid biopsy, whereas the reference standard was the conventional tissue biopsy. The target condition was the detection of <i>BRAF V600E</i> mutation. The study population consisted of individuals with ameloblastoma recruited from three tertiary hospitals from Brazil. A negative control group composed of three individuals with confirmed wild-type <i>BRAF</i> lesions were included. The participants underwent plasma circulating cell-free DNA and tumor tissue DNA isolation, and both were submitted to using competitive allele-specific TaqMan™ real-time polymerase chain reaction technology mutation detection assays. Sensitivity and specificity measures and positive and negative predictive values were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twelve patients with conventional ameloblastoma were included. <i>BRAF V600E</i> mutation was detected in 11/12 (91.66%) ameloblastoma tissue samples. However, the mutation was not detected in any of the plasma-based liquid biopsy circulating cell-free DNA samples in both ameloblastomas and negative control group. The sensitivity and specificity of plasma-based liquid biopsy for the detection of the <i>BRAF V600E</i> mutation in circulating cell-free DNA was 0.0 and 1.0, respectively. The agreement between index test and reference standard results was 26.66%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Plasma-based liquid biopsy does not seem to be an accurate method for the detection of the <i>BRAF V600E</i> mutation in circulating circulating cell-free DNA from patients with ameloblastoma, regardless of tumor size, anatomic location, recurrence status, and other clinicopathological features.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 4","pages":"258-265"},"PeriodicalIF":3.3,"publicationDate":"2024-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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