Translation of mouse model to human gives insights into periodontitis etiology

To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10-4), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10-5) and RNASE2 (rs2771342, P = 2.84×10-5) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10-14) and HLA-DPA1 (rs17214512, P = 5.14×10-5). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease

Epigenetic Alterations Associated with the Overall Survival and Recurrence Free Survival among Oral Squamous Cell Carcinoma Patients

Oral squamous cell carcinoma (OSCC) is a fatal disease caused by complex interactions between environmental, genomic, and epigenetic alterations. In the current study, we aimed to identify clusters of genes whose promoter methylation status correlated with various tested clinical features. Molecular datasets of genetic and methylation analysis based on whole-genome sequencing of 159 OSCC patients were obtained from the The Cancer Genome Atlas (TCGA) data portal. Genes were clustered based on their methylation status and were tested for their association with demographic, pathological, and clinical features of the patients. Overall, seven clusters of genes were revealed that showed a significant association with the overall survival/recurrence free survival of patients. The top ranked genes within cluster 4, which showed the worst prognosis, primarily acted as paraneoplastic genes, while the genes within cluster 6 primarily acted as anti-tumor genes. A significant difference was found regarding the mean age in the different clusters. No significant correlation was found between the tumor staging and the different clusters. In conclusion, our result provided a proof-of-principle for the existence of phenotypic diversity among the epigenetic clusters of OSCC and demonstrated the utility of the use epigenetics alterations in devolving new prognostic and therapeutics tools for OSCC patients

Three-Dimensional Technology Applications in Maxillofacial Reconstructive Surgery: Current Surgical Implications

Defects in the oral and maxillofacial (OMF) complex may lead to functional and esthetic impairment, aspiration, speech difficulty, and reduced quality of life. Reconstruction of such defects is considered one of the most challenging procedures in head and neck surgery. Transfer of different auto-grafts is still considered as the “gold standard” of regenerative and reconstructive procedures for OMF defects. However, harvesting of these grafts can lead to many complications including donor-site morbidity, extending of surgical time, incomplete healing of the donor site and others. Three-dimensional (3D) printing technology is an innovative technique that allows the fabrication of personalized implants and scaffolds that fit the precise anatomy of an individual’s defect and, therefore, has attracted significant attention during the last few decades, especially among head and neck surgeons. Here we discuss the most relevant applications of the 3D printing technology in the oral and maxillofacial surgery field. We further show different clinical examples of patients who were treated at our institute using the 3D technology and discuss the indications, different technologies, complications, and their clinical outcomes. We demonstrate that 3D technology may provide a powerful tool used for reconstruction of various OMF defects, enabling optimal clinical results in the suitable cases

Towards system genetics analysis of head and neck squamous cell carcinoma using the mouse model, cellular platform, and clinical human data

Abstract Head and neck squamous cell cancer (HNSCC) is a leading global malignancy. Every year, More than 830 000 people are diagnosed with HNSCC globally, with more than 430 000 fatalities. HNSCC is a deadly diverse malignancy with many tumor locations and biological characteristics. It originates from the squamous epithelium of the oral cavity, oropharynx, nasopharynx, larynx, and hypopharynx. The most frequently impacted regions are the tongue and larynx. Previous investigations have demonstrated the critical role of host genetic susceptibility in the progression of HNSCC. Despite the advances in our knowledge, the improved survival rate of HNSCC patients over the last 40 years has been limited. Failure to identify the molecular origins of development of HNSCC and the genetic basis of the disease and its biological heterogeneity impedes the development of new therapeutic methods. These results indicate a need to identify more genetic factors underlying this complex disease, which can be better used in early detection and prevention strategies. The lack of reliable animal models to investigate the underlying molecular processes is one of the most significant barriers to understanding HNSCC tumors. In this report, we explore and discuss potential research prospects utilizing the Collaborative Cross mouse model and crossing it to mice carrying single or double knockout genes (e.g. Smad4 and P53 genes) to identify genetic factors affecting the development of this complex disease using genome‐wide association studies, epigenetics, microRNA, long noncoding RNA, lncRNA, histone modifications, methylation, phosphorylation, and proteomics

Dissecting the Complexity of Skeletal-Malocclusion Associated Phenotypes: Mouse for the Rescue

Skeletal deformities and malocclusions being heterogeneous traits, affect populations worldwide, resulting in compromised esthetics and function and reduced quality of life. Skeletal Class III prevalence is the least common of all angle malocclusion classes, with a frequency of 7.2%, while Class II prevalence is approximately 27% on average, varying in different countries and between ethnic groups. Orthodontic malocclusions and skeletal deformities have multiple etiologies, often affected and underlined by environmental, genetic and social aspects. Here, we have conducted a comprehensive search throughout the published data until the time of writing this review for already reported quantitative trait loci (QTL) and genes associated with the development of skeletal deformation-associated phenotypes in different mouse models. Our search has found 72 significant QTL associated with the size of the mandible, the character, shape, centroid size and facial shape in mouse models. We propose that using the collaborative cross (CC), a highly diverse mouse reference genetic population, may offer a novel venue for identifying genetic factors as a cause for skeletal deformations, which may help to better understand Class III malocclusion-associated phenotype development in mice, which can be subsequently translated to humans. We suggest that by performing a genome-wide association study (GWAS), an epigenetics-wide association study (EWAS), RNAseq analysis, integrating GWAS and expression quantitative trait loci (eQTL), micro and small RNA, and long noncoding RNA analysis in tissues associated with skeletal deformation and Class III malocclusion characterization/phenotypes, including mandibular basic bone, gum, and jaw, in the CC mouse population, we expect to better identify genetic factors and better understand the development of this disease

Dissecting the Complexity of Skeletal-Malocclusion-Associated Phenotypes: Mouse for the Rescue

Skeletal deformities and malocclusions being heterogeneous traits, affect populations worldwide, resulting in compromised esthetics and function and reduced quality of life. Skeletal Class III prevalence is the least common of all angle malocclusion classes, with a frequency of 7.2%, while Class II prevalence is approximately 27% on average, varying in different countries and between ethnic groups. Orthodontic malocclusions and skeletal deformities have multiple etiologies, often affected and underlined by environmental, genetic and social aspects. Here, we have conducted a comprehensive search throughout the published data until the time of writing this review for already reported quantitative trait loci (QTL) and genes associated with the development of skeletal deformation-associated phenotypes in different mouse models. Our search has found 72 significant QTL associated with the size of the mandible, the character, shape, centroid size and facial shape in mouse models. We propose that using the collaborative cross (CC), a highly diverse mouse reference genetic population, may offer a novel venue for identifying genetic factors as a cause for skeletal deformations, which may help to better understand Class III malocclusion-associated phenotype development in mice, which can be subsequently translated to humans. We suggest that by performing a genome-wide association study (GWAS), an epigenetics-wide association study (EWAS), RNAseq analysis, integrating GWAS and expression quantitative trait loci (eQTL), micro and small RNA, and long noncoding RNA analysis in tissues associated with skeletal deformation and Class III malocclusion characterization/phenotypes, including mandibular basic bone, gum, and jaw, in the CC mouse population, we expect to better identify genetic factors and better understand the development of this disease

Clinical and Prognostic Significance of the Eighth Edition Oral Cancer Staging System

Objectives: The most notable changes in the eighth edition of the AJCC Cancer Staging System include incorporating the depth of invasion (DOI) into T staging and extranodal extension (ENE) into N staging. In this study, we retrospectively assessed the prognostic and clinical implications of the eighth TNM staging system. Materials and Methods: Patients with Oral Squamous Cell Carcinoma (OSCC) who were treated surgically between 2010 and 2017 were retrospectively reviewed. Tumors were first staged according to the seventh edition and restaged using the eighth edition. The prognostic value of the resultant upstaging was evaluated. Results: Integrating the DOI into the T classification resulted in the upstaging of 65 patients, whereas incorporating ENE into the N staging resulted in the upstaging of 18 patients (p p > 0.05). Conclusion: Our results demonstrate the importance of incorporating ENE into nodal staging and considering adjuvant therapy when ENE is present