Effects of single unilaterally impacted mesiodens on maxillary central incisors: A 3D quantitative assessment based on cone-beam computed tomography.

BACKGROUND: Mesiodens usually lead to the malposition and abnormal morphology of maxillary central incisors. AIM: To evaluate the detrimental effects of single unilaterally impacted mesiodens on the three-dimensional positions and morphology of the maxillary central incisor using cone-beam computed tomographic (CBCT) examinations. DESIGN: A total of 321 patients aged 5-17 years with single unilaterally impacted mesiodens were included and divided into two groups: mixed dentition group (5-10 years) and early permanent dentition group (11-17 years). CBCT data for these patients were retrospectively analyzed to compare the inclination, rotation, angulation, and morphology of maxillary central incisors between the affected and contralateral control sides. The morphology, orientation, and spatial location of mesiodens were also assessed. RESULTS: Central incisors on the affected side showed significant palatal crown inclination, shorter root, shorter tooth, and greater crown-to-root ratio in both groups, whereas significant mesial crown angulation was only observed in the mixed dentition group. CONCLUSION: Impacted mesiodentes result in the displacement and impaired root development of central incisors, strongly suggesting timely clinical management of these abnormal teeth, such as the early removal of mesiodens and orthodontic treatments.

Development of a novel prognostic signature derived from essential genes in head and neck squamous cell carcinoma.

BACKGROUND: Substantial heterogeneity in head and neck squamous cell carcinoma (HNSCC) compromise accurate patient stratification and personalized treatment planning. Current molecular classification is largely based on genes with highly variable expression without considering their functional roles. Here, we sought to identify HNSCC essential genes for patient stratification and prognostication. METHODS: Essential genes for HNSCC were screened from genome-wide CRISPR knockout datasets. Candidates were further identified through univariate Cox regression. The least absolute shrinkage and selection operator was utilized to develop the prognostic signature. Candidate essential genes were exploited to classify patients into subgroups by consensus clustering. Survival outcomes, genomic alterations, signaling activities, and therapeutic vulnerabilities were compared between patient subgroups. RESULTS: Sixty-eight genes were identified as candidates and utilized to develop an 8-gene prognostic signature. Patients were segregated into two clusters with distinct survival rates across multiple cohorts based on upregulated essential genes. Cluster 2 exhibited higher TP53, CDKN2A, and NOTCH1 mutations, higher stromal activities, worse prognosis as well as and sensitivities to cell cycle inhibitors. Cluster 1 was characterized by a better prognosis and susceptibility to PI3K/AKT and MAPK inhibitors. CONCLUSION: Our study developed a novel and robust prognostic signature and classification derived from essential genes for HNSCC, which sheds new light on HNSCC precision oncology.

Characterizations of three-dimensional root morphology and topological location of mandibular third molars by cone-beam computed tomography.

PURPOSE: This study aimed to delineate three-dimensional (3D) root morphology and topological locations of mandibular third molars (MTMs) by cone-beam computed tomography (CBCT) in a Chinese adult dental population. METHODS: Adult patients with MTMs were retrospectively screened based on CBCT images at our institution between January 2018 and December 2019. Root morphology and spatial locations of these teeth were defined based on CBCT 3D images. Potential associations with epidemiological and clinical/radiological parameters were analyzed using Chi-square or Fisher exact test. Two-tailed P values less than 0.05 were considered statistically significant. RESULTS: A total number of 2680 eligible patients (male/female:0.74; 35 ± 10 years old) with 4180 MTMs were enrolled. The majority of MTMs had 2 roots 3064 (73.30%), followed by 800 (19.14%) 1 root, 302 (7.22%) 3 roots, and 14 (0.33%) 4 roots. More than half of one-rooted MTMs were convergent, followed by club-shaped and C-shaped. Among MTMs with 2 roots, 2860 (93.34%) were M-D (mesio-distal) types. Most MTMs with 3 roots were M-2D (one root in mesial, two roots in distal) types, followed by 2M-D (two roots in mesial, one root in distal) types, and B-2L (one root in buccal, two roots in lingual) types. The presence of root configurations was significantly associated with the angulation, depth, and width classification in two-rooted MTMs (P < 0.05). CONCLUSIONS: Although the morphology and spatial locations of MTMs vary greatly, our results from a large dental population reconfirm that most MTMs have two roots with mesial-distal type of spatial distribution.

Comprehensive characterization of epidemiological and 3D radiographic features of non-third molar impacted teeth in a Chinese dental population.

OBJECTIVE: This retrospective study aimed to comprehensively delineate the epidemiological and 3-dimensional radiographic characteristics of non-third molar (non-M3) impacted teeth in a Chinese dental population. MATERIAL AND METHODS: Patients with impacted teeth except for the third molar (ITEM3) were retrospectively screened via cone-beam CT images from 75,021 patients treated at our institution from June 2012 to December 2018. Demographic and clinical data of patients with ITEM3 were retrieved from medical records. CBCT coupled with 3-dimensional reconstruction was employed to characterize the radiographic features of ITEM3. Associations between these epidemiological, clinical, and radiographic features were further statistically analyzed. RESULTS: Among 1975 eligible patients, 2467 ITEM3s were identified with a prevalence of 2.63% (1975/75,021). Females slightly outnumbered males with a ratio of 1.12:1. The majority of ITEM3 was single (1577, 79.85%) in the maxilla. The maxillary canine teeth were the most frequently impacted (52.45%), followed by maxillary incisors. The mesioangular position was the most common orientation (43.8%), followed by vertical and buccal-lingual orientations. The most frequently associated lesion was external root resorption of the adjacent tooth, which was significantly correlated with the morphology and position of the impacted tooth. CONCLUSION: Most ITEM3 was single, mesioangular, found at maxillary canines, sometimes associated with diverse complications. Our data advance the current understanding of ITEM3 and offer insights into the management of this dental abnormality. CLINICAL RELEVANCE: These findings are useful for clinicians to comprehensively understand the prevalence, radiographic features, and complications of non-M3 impacted teeth.

Epidemiological, clinical, radiographic characterization of non-syndromic supernumerary teeth in Chinese children and adolescents.

OBJECTIVE: This retrospective study was purposed to evaluate epidemiological, clinical, and 3D radiological features of supernumerary teeth (ST) in a non-syndromic Chinese children and adolescent dental population. MATERIALS AND METHODS: Original cone-beam CT (CBCT) data from 18,861 patients aged from 6 to 17 years with dental maxillofacial diseases treated in a Chinese dental hospital from June 2012 to December 2018 were utilized to screen patients with ST. Diagnosis and characterizations of ST were analyzed by CBCT coupled with 3D reconstruction. All relevant epidemiological, clinical, and radiographic details about ST were collected and statistically analyzed. RESULTS: Among total 18,861 patients, 2,768 ST were identified in 1984 subjects with a prevalence of 10.52% and a male:female ratio of 1.86:1. Majority of ST were single, conical, inverted, impacted, and located in maxilla anterior region. ST-associated complications mainly included malposition, rotation, and impaction of adjacent teeth, which were notably associated with morphology and position of ST. CONCLUSION: The prevalence of ST in Chinese children and adolescent dental population was 10.52% and tended to present as single, conical, inverted, and impacted, which resulted in abnormalities of neighboring teeth. Our outcomes are beneficial for clinicians to more comprehensively understand the incidence, characterization, and clinical treatment planning of ST in dental children and adolescents.

Identification of a prognostic alternative splicing signature in oral squamous cell carcinoma.

Alternative splicing (AS) is critically associated with tumorigenesis and patient's prognosis. Here, we systematically analyzed survival-associated AS signatures in oral squamous cell carcinoma (OSCC) and evaluated their prognostic predictive values. Survival-related AS events were identified by univariate and multivariate Cox regression analyses using OSCC data from the TCGA head neck squamous cell carcinoma data set. The Percent Spliced In calculated by SpliceSeq from 0 to 1 was used to quantify seven types of AS events. A predictive model based on AS events was constructed by least absolute shrinkage and selection operator Cox regression assay and further validated using a training-testing cohort design. Patient survival was estimated using the Kaplan-Meier method and compared with Log-rank test. The receiver operating characteristics curve area under the curves was used to evaluate the predictive abilities of these predictive models. Furthermore, gene-gene interaction networks and the splicing factors (SFs)-AS regulatory network was generated by Cytoscape. A total of 825 survival-related AS events within 719 genes were identified in OSCC samples. The integrative predictive model was better at predicting outcomes of patients as compared to those models built with the individual AS event. The predictive model based on three AS-related genes also effectively predicted patients' survival. Moreover, seven survival-related SFs were detected in OSCC including RBM4, HNRNPD, and HNRNPC, which have been linked to tumorigenesis. The SF-AS network revealed a significant correlation between survival-related AS genes and these SFs. Our findings revealed a systemic portrait of survival-associated AS events and the splicing network in OSCC, suggesting that AS events might serve as novel prognostic biomarkers and therapeutic targets for OSCC.

Therapeutically targeting head and neck squamous cell carcinoma through synergistic inhibition of LSD1 and JMJD3 by TCP and GSK-J1.

BACKGROUND: The histone demethylase LSD1 is a key mediator driving tumorigenesis, which holds potential as a promising therapeutic target. However, treatment with LSD1 inhibitors alone failed to result in complete cancer regression. METHODS: The synergistic effects of TCP (a LSD1 inhibitor) and GSK-J1 (a JMJD3 inhibitor) against HNSCC were determined in vitro and in preclinical animal models. Genes modulated by chemical agents or siRNAs in HNSCC cells were identified by RNA-seq and further functionally interrogated by bioinformatics approach. Integrative siRNA-mediated gene knockdown, rescue experiment and ChIP-qPCR assays were utilised to characterise the mediators underlying the therapeutic effects conferred by TCP and GSK-J1. RESULTS: Treatment with TCP and GSK-J1 impaired cell proliferation, induced apoptosis and senescence in vitro, which were largely recapitulated by simultaneous LSD1 and JMJD3 knockdown. Combinational treatment inhibited tumour growth and progression in vivo. Differentially expressed genes modulated by TCP and GSK-J1 were significantly enriched in cell proliferation, apoptosis and cancer-related pathways. SPP1 was identified as the mediator of synergy underlying the pro-apoptosis effects conferred by TCP and GSK-J1. Co-upregulation of LSD1 and JMJD3 associated with worse prognosis in patients with HNSCC. CONCLUSIONS: Our findings revealed a novel therapeutic strategy of simultaneous LSD1 and JMJD3 inhibition against HNSCC.

Predictive value of prognostic nutritional index in patients with oral squamous cell carcinoma.

OBJECTIVES: To determine the prognostic significance of preoperative prognostic nutritional index (PNI) in patients with primary oral squamous cell carcinoma (OSCC) after ablative surgery. MATERIALS AND METHODS: A total of 333 patients from two tertiary referral centers were enrolled as training and validation cohorts. The PNI was calculated as 10× serum albumin (g/dL) + 0.005 × total lymphocyte number (per mm3 ), and its optimal cutoff value for patient stratification was identified by X-tile software. Cox's proportional regression analyses and receiver operating characteristic (ROC) curves were employed to identify prognostic factors and their predictive performance. RESULTS: The optimal cutoff value of PNI was 47.4. Patients with low PNI had significantly shorter overall (OS) and disease-free survival than those with high PNI. Moreover, multivariate regression analyses indicated that PNI was an independent prognostic factor for OS in the training (hazard ratio [HR], 2.267; 95% confidence interval [CI]:1.335-3.849; p = .002) and validation (HR, 2.247; 95% CI: 1.352-3.735; p = .002) cohorts. ROC analyses revealed similar or superior predictive performance of PNI as compared to other prognostic parameters. CONCLUSIONS: Our findings reveal that decreased preoperative PNI significantly associates with worse prognosis for patients with OSCC, which serves as a novel prognostic biomarker for OSCC.

Epidemiological, clinical, and 3-dimentional CBCT radiographic characterizations of supernumerary teeth in a non-syndromic adult population: a single-institutional study from 60,104 Chinese subjects.

OBJECTIVE: This study was aimed to delineate the prevalence, clinical, and 3-dimentional radiographic characteristics of adult supernumerary teeth (ST found) in a Chinese non-syndromic, dental population. MATERIALS AND METHODS: Medical records and cone beam computed tomography (CBCT) images were utilized to identify adult patients with ST in a tertiary referral dental hospital between June 2012 and December 2018. CBCT scan coupled with 3-dimentional reconstruction was used to characterize the detailed location, morphology, orientation of ST, and their relationship with adjacent teeth and neighboring structures. All relevant information regarding age and gender of patients, morphology, and 3-dimentional topography of ST as well as ST-associated complications were recorded and statistically analyzed. RESULTS: A total number of 1149 ST was identified in 921 eligible patients screened from 60,104 subjects with the prevalence of 1.5%. Male patients outnumbered females with a gender ratio of 1.76:1. The majority of ST was single, located in the maxilla, especially the maxillary central incisor region. Most ST were conical shape, inverted orientation, and impacted. ST-associated complications including impaction or root resorption of adjacent teeth, and cystic/tumor-like lesions were totally found in 13% ST and significantly associated with location, orientation, and morphology of ST. CONCLUSIONS: Most ST in Chinese adults were conical, inverted, impacted, and located in the maxillary central incisor region, and associated with various complications. Our findings offer valuable information concerning the prevalence, clinical, and radiographic characteristics of ST in non-syndromic Chinese adults. CLINICAL RELEVANCE: These findings are beneficial for clinicians to comprehensively understand the incidence, pathogenesis, and clinical management of ST.

Comprehensive Analyses of Intraoral Benign and Malignant Nerve Sheath Tumors: The Rare Disease Entities Revisited.

INTRODUCTION: Intraoral benign and malignant nerve sheath tumors (BNST and MNST) are rare tumors with non-specific clinical presentations and represent diagnostic and therapeutic challenges. Current knowledge regarding their demographic, clinicopathological features and treatments remains fragmented. MATERIALS AND METHODS: The original data about patients diagnosed as intraoral BNST and MNST were retrieved from our disease registry (2005-2017). Comprehensive reviews of English and Chinese literature were performed to collect and analyze the epidemiological, clinicopathological data and treatment outcomes about those published cases. RESULTS: Thirty-four intraoral BNSTs were found at our institution in the past 13 years. Literature reviews identified 354 intraoral BNSTs in 223 articles and 60 intraoral MNSTs in 50 articles. Most intraoral BNSTs and MNSTs were presented in the second to fifth decade of life. Males outnumbered females in MNSTs, while BNSTs displayed a slight female preponderance. The common sites for intraoral BNSTs were parapharyngeal space followed by tongue, whereas mandible was the most common site for MNSTs. Most intraoral BNSTs were presented as slow-growing, painless mass or swelling, while MNSTs usually appeared as painful and invasive mass with discomfort. Surgical excision was preferred for intraoral BNSTs with excellent prognosis. Complete resection was indicated for intraoral MNST with dismal prognosis as evidenced by much recurrence, metastasis, and death. CONCLUSION: Intraoral BNST and MNST are rare diseases which should not be ignored when intraoral painless or painful mass/swelling is found. Surgical excision is indicated for intraoral BNST with favorable outcomes. However, further investigations are warranted to optimize the treatment for intraoral MNST to improve its prognosis.

SUZ12 is a novel putative oncogene promoting tumorigenesis in head and neck squamous cell carcinoma.

The suppressor of zest 12 (SUZ12), one of the core polycomb repressive complex 2 (PRC2) components, has increasingly appreciated as a key mediator during human tumorigenesis. However, its expression pattern and oncogenic roles in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored yet. Here, we sought to determine its expression pattern, clinicopathological significance and biological roles in HNSCC. Through data mining and interrogation from multiple publicly available databases, our bioinformatics analyses revealed that SUZ12 mRNA was significantly overexpressed in multiple HNSCC patient cohorts. Moreover, SUZ12 protein was markedly up-regulated in primary HNSCC samples from our patient cohort as assessed by immunohistochemical staining and its overexpression significantly associated with cervical node metastasis and reduced overall and disease-free survival. In the 4-nitroquinoline 1-oxide (4NQO)-induced HNSCC mouse model, increased SUZ12 immunostaining was observed along with disease progression from epithelial hyperplasia to squamous cell carcinoma in tongue. Furthermore, shRNA-mediated SUZ12 knock-down significantly inhibited cell proliferation, migration and invasion in HNSCC cells, and resulted in compromised tumour growth in vivo. Collectively, our data reveal that SUZ12 might serve as a putative oncogene by promoting cell proliferation, migration and invasion, and also a novel biomarker with diagnostic and prognostic significance for HNSCC.

TEAD4 overexpression promotes epithelial-mesenchymal transition and associates with aggressiveness and adverse prognosis in head neck squamous cell carcinoma.

BACKGROUND: Deregulated Hippo signaling has been uncovered to be intricately involved in tumorigenesis. Transcriptional factor TEADs serve as key mediators of Hippo signaling and have been increasingly appreciated as putative oncogenes driving cancer initiation and progression. However, its expression pattern and oncogenic role of TEAD4 in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. METHODS: TEAD4 mRNA expression in HNSCC was determined by data mining and analyses from TCGA dataset and four independent cohorts with transcriptional profiling data publically available. The protein abundance of TEAD4 was measured by immunohistochemistry in 105 primary HNSCC samples and associations between its expression and clinicopathological parameters and patient survival were evaluated. The oncogenic roles of TEAD4 was further determined by 4-nitroquinoline 1-oxide (4NQO)-induced animal model, both knockdown/overexpression assay and TGF-ß1-induced epithelia-mesenchymal transition (EMT) in vitro. RESULTS: Both mRNA and protein abundance of TEAD4 were significantly increased in HNSCC as compared to its non-tumor counterparts. Overexpression of TEAD4 significantly associated with high pathological grade, cervical node metastasis, advanced clinical stage and reduced overall and disease-free survival. In the 4NQO-induced HNSCC mouse model, increased TEAD4 immunostaining was found associated with disease progression. TEAD4 knockdown significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis in HNSCC cells, while its overexpression resulted in opposite effects and EMT. Moreover, TEAD4 was critically involved in TGF-ß1-induced EMT in HNSCC cells. CONCLUSIONS: Our findings reveal that TEAD4 serves as a novel prognostic biomarker and putative oncogene for HNSCC by promoting cell proliferation, migration and invasion, and EMT.

Overexpression of WD repeat domain 5 associates with aggressive clinicopathological features and unfavorable prognosis in head neck squamous cell carcinoma.

BACKGROUND: WD repeat domain 5 (WDR5), a core member of Mixed lineage leukemia (MLL) and SET1 histone H3 lysine 4 (H3K4) methyltransferase complexes, is involved in multiple biological and pathological processes. Its deregulation in cancer and pro-tumorigenic roles has been increasingly appreciated. However, the expression pattern of WDR5 and its biological functions in head neck squamous cell carcinoma (HNSCC) have not been well established. METHODS: The expression of WDR5 mRNA in HNSCC was determined by data mining and interrogation using publicly available databases. Its protein expression was measured by immunohistochemistry in a retrospective cohort of primary HNSCC samples. Moreover, the associations between WDR5 expression and various clinicopathological parameters and patient survival were assessed. The pro-tumorigenic roles of WDR5 in HNSCC were further delineated in vitro by loss-of-function assay. RESULTS: Our bioinformatics analyses revealed that WDR5 mRNA was significantly overexpressed in 3 HNSCC cohorts. WDR5 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with large tumor size, advanced clinical stage (chi-square test, P = .048, .006) and reduced overall and disease-free survival (Kaplan-Mier analyses, Log-rank test, P = .0137, .0154). Univariate and multivariate survival analyses further revealed WDR5 protein abundance as an independent prognostic factor for patients' overall survival. Moreover, WDR5 knockdown significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis in HNSCC cells. CONCLUSIONS: Our findings reveal that WDR5 is aberrantly overexpressed in HNSCC and associates with aggressiveness and unfavorable prognosis, thus representing a novel diagnostic and prognostic biomarker for HNSCC.

Density and location of CD3+ and CD8+ tumor-infiltrating lymphocytes correlate with prognosis of oral squamous cell carcinoma.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are regarded as adaptive immune response of the host to cancer cells and valuable prognostic factors. Here, we sought to characterize the densities and locations of CD3+ and CD8+ TILs in primary oral squamous cell carcinoma (OSCC) samples and assess their clinicopathological and prognostic significance. METHODS: A total number of 169 OSCC samples from 2 independent patient cohorts (Nanjing cohort, 93 cases; Wuxi cohort, 76 cases) were retrospectively collected. The numbers of CD3+ and CD8+ TILs at tumor center (CT) and invasive margin (IM) of OSCC were identified by immunohistochemistry and calculated. The optimal cutoff values for CD3+ and CD8+ TILs to stratify patients were determined by X-tile software in Nanjing cohort and further utilized in Wuxi cohort. The associations between CD3+ /CD8+ TILs and clinicopathological parameters or patient survival were assessed. The prognostic values of CD3+ / CD8+ TILs were evaluated by Cox regression analyses. RESULTS: CD3+ and CD8+ TILs were identified at both CT and IM and enriched at IM. High density of CD3+ TILs at IM (CD3 IM) was significantly associated with increased overall and disease-specific survival (P < .05). High density of CD8+ TILs at CT (CD8 CT) was significantly associated with increased overall but not disease-specific survival. Moreover, CD3 IM and CD8 CT were identified as independent prognostic factors for patient survival. CONCLUSIONS: Our findings provide further evidence to support the prognostic values of CD3+ and CD8+ TILs for OSCC, suggesting that TIL subsets might be viable biomarkers and therapeutic targets with translational significance.

Comprehensive analysis of 225 Castleman's diseases in the oral maxillofacial and neck region: a rare disease revisited.

OBJECTIVES: The aim of the present study was to comprehensively summarize the epidemiological, clinicopathological characteristics, treatments as well as prognosis of Castleman's disease (CD) identified in the oral maxillofacial and neck region. MATERIALS AND METHODS: Patients with CD in the oral maxillofacial and neck were retrieved from disease registry at our institution from Jan. 1990 to Dec. 2015. Systematic reviews from both English and Chinese literature were performed to collect the detailed information about the oral maxillofacial and neck CD. The epidemiological, clinicopathological data and treatment outcomes were further statistically analyzed. RESULTS: Four patients with the oral maxillofacial and neck CD were identified and histologically confirmed as hyaline-vascular type. They underwent surgical excision without recurrence during the follow-up. Systematic literature reviews identified 221 cases from 123 eligible articles which satisfied the inclusion criteria. In 225 patients, most patients were diagnosed as unicentric (207) or hyaline-vascular type (205) of CD and identified in the neck, and treated by surgical resection with good prognosis. In contrast, the minority of patients was multicentric or plasma-cell/mixed type and treated by chemotherapy with inferior outcomes. Kaplan-Meir analyses revealed that both clinical and pathological types were significantly associated with patients' overall survival. CONCLUSIONS: Although rare, most cases of the oral maxillofacial neck CD are found in adults and classified as unicentric and hyaline-vascular type of CD. Complete surgical excision is preferred with favorable prognosis for unicentric disease, whereas chemotherapy is usually exploited for multicentric disease with inferior outcomes. CLINICAL RELEVANCE: These data provide comprehensive information about the epidemiology, clinicopathological features, treatments, and outcomes of the oral maxillofacial and neck CD.

Overexpression of suppressor of zest 12 is associated with cervical node metastasis and unfavorable prognosis in tongue squamous cell carcinoma.

OBJECTIVE: Increased expression of suppressor of zest 12 (SUZ12), a core component of the polycomb repressive complex 2, contributes to human tumorigenesis and associates with patient prognosis. In the present study, we sought to investigate the expression of SUZ12 and its clinicopathological significance in primary tongue squamous cell carcinoma (TSCC). METHODS: The expression of SUZ12 protein was determined by immunohistochemistry in clinical samples from a retrospective cohort of 72 patients with primary TSCC who were treated at our institution from Jan. 2007 to Dec. 2013. The potential associations between SUZ12 abundance and multiple clinicopathological parameters were assessed by Chi square test. Moreover, the effect of SUZ12 expression on patients' survival was further estimated by Kaplan-Meier and Cox regression analyses. RESULTS: Our immunohistochemical staining data revealed aberrant overexpression of SUZ12 in a large subset of TSCC as compared to normal tongue mucosa. Elevated SUZ12 was found to be significantly associated with cervical nodes metastasis (P = 0.0325) and reduced overall as well as disease-free survival (Log-rank test, P = 0.0225, 0.0179, respectively). Both univariate and multivariate Cox regression analysis identified the expression status of SUZ12 (low/high) as an important independent prognostic factor for patients' survival. CONCLUSIONS: Our data reveal that aberrant SUZ12 overexpression is associated with cervical nodes metastasis and reduced survival in TSCC. These findings suggest that SUZ12 might play critical roles during tongue tumorigenesis and serve as a novel biomarker with diagnostic and prognostic significance.

External root resorption of the second molar associated with mesially and horizontally impacted mandibular third molar: evidence from cone beam computed tomography.

OBJECTIVES: The aim of the present study was to assess the incidence and risk factors of ERR in second molars with mesially and horizontally impacted mandibular third molars using cone beam computed tomography (CBCT) images from patients in a Chinese tertiary referral hospital. MATERIALS AND METHODS: A total number of 216 patients with 362 mesially and horizontally impacted mandibular third molars who were treated at our institution from 2014 to 2015 was retrospectively included. The ERR in second molars was identified on CBCT multiplanar images. The associations between incidence of ERR and multiple clinical parameters were statistically analyzed by Chi-square test. Moreover, the risk factors for ERR in second molars were further assessed by multivariate regression analysis. RESULTS: The overall incidence of ERR in second molars was 20.17 % (73/362) as detected on CBCT images. The presence of ERR significantly associated with patients age and impaction depth of mandibular third molars. However, no significant relationship was found between ERR severity and impaction depth or ERR location. Multivariate regression analyses further revealed age over 35 years and impaction depth as important risk factors affecting the ERR incidence caused by mesial and horizontal impaction of mandibular third molar. CONCLUSIONS: ERR in second molar resulted from mesially and horizontally impacted mandibular third molar is not very rare and can be reliably identified via CBCT scan. CLINICAL RELEVANCE: Given the possibility of ERR associated with third molar impaction, the prophylactic removal of these impacted teeth could be considered especially for those patients with over 35 years and mesially and horizontally impacted teeth.

The pluripotency factor LIN28B is involved in oral carcinogenesis and associates with tumor aggressiveness and unfavorable prognosis.

OBJECTIVE: LIN28B is a conserved RNA-binding protein critically involved in development, cellular metabolism and tumorigenesis. It is frequently overexpressed in human cancers and correlates with tumor aggressiveness as well as unfavorable prognosis. However, the expression pattern and oncogenic roles of LIN28B during oral squamous cell carcinoma (OSCC) development and progression has not been well established yet. Here, we sought to determine the expression of LIN28B and its clinical significance using chemical-induced OSCC animal model, cell lines and primary specimens. METHOD: The OSCC animal model was induced using 7,12-dimethyl-1,2-bezan-tracene (DMBA) painting in the hamster buccal pouch. Buccal lesions from animals were obtained from different time points and subjected to routine histological analyses and immunohistochemical staining of LIN28B. The mRNA, protein abundance and subcellular localization of LIN28B was determined in a panel of OSCC cell lines by real-time RT-PCR, western blot and immunofluorescence. The expression levels of LIN28B in human primary OSCC samples were further evaluated by immunohistochemical staining. Moreover, the relationship between LIN28B and several clinicopathological parameters as well as patients' prognosis were also assessed. RESULTS: Our results revealed that negative or low LIN28B expression was commonly observed in normal epithelial, whereas more LIN28B abundance was identified in epithelial dysplasia and invasive SCC in the DMBA-induced OSCC animal model. Overexpression of LIN28B was identified in a major fraction of OSCC samples(39/58) and significantly associated with tumor size (P = 0.049) and advanced clinical stages (P = 0.0286). Patients with increased LIN28B had markedly reduced overall survival as compared to those with low LIN28B. Multivariate survival analyses further indicated that LIN28B abundance served as an independent prognostic factor for patients' overall survival. CONCLUSIONS: Our findings reveal that LIN28B is critically involved in OSCC initiation and progression and aberrantly overexpressed in human OSCC. It might represent a novel diagnostic and prognostic biomarker for oral cancer.

Reconstruction of palatomaxillary defects following cancer ablation with temporalis muscle flap in medically compromised patients: a 15-year single institutional experience.

OBJECTIVES: Successful reconstruction of palatomaxillary defects following cancer ablation represents a formidable challenge for surgeons to achieve consistently favorable outcomes. The purpose of this article is to present our experience in oncologic palatomaxillary repair with temporalis muscle flap (TMF) for medically compromised patients who are not ideal candidates for microvascular reconstruction at a Chinese tertiary referral hospital over a 15-year period (1998-2012). METHOD: A retrospective chart review was performed to identify patients with compromised medical conditions who underwent oncologic palatomaxillary reconstruction using TMF. Patients' demographics, clinicopathological variables, and surgical techniques were presented. Postoperative functional and aesthetic outcomes were assessed by measurements and patients self-evaluations. RESULTS: Sixty-nine TMFs were successfully harvested and used for immediate oncologic palatomaxillary reconstruction in 67 patients (31 males and 36 females, mean age 60.4 years) with diverse primary malignancies. These patients' co-morbidities included systemic diseases, preoperative chemotherapy/radiotherapy, and elder over 65 years which precluded the ideal utility of free flaps. Fifty-one patients remained alive without disease, while nine had recurrences/metastases and seven died during the follow-up (0.5-10.4 years, mean 3.7 years). All flaps survived with only partial necroses in four cases. Complications and donor-site morbidities were minimal with five transient facial paralysis and four mild diplopia and enophthalmos. Unrestricted diet and mouth opening, intelligible speech, and satisfactory temporal aesthetics were obtained in most patients. CONCLUSION: The TMF is a reliable, versatile, and alternative option for oncologic palatomaxillary reconstruction with satisfactory functional and aesthetic outcomes and minimal complications, especially when appropriately selected for those medically compromised patients.

The top 100 highly cited articles on surgery-first orthognathic surgery between 2009 and 2022: a bibliometric and visualized analysis.

OBJECTIVES: To reveal research focuses on surgery-first orthognathic surgery by a bibliometric and visualized analysis of the top 100 highly cited articles. STUDY DESIGN: Published papers related to surgery-first orthognathic surgery were retrospectively retrieved from the Web of Science Core Collection from 2009 to 2022. The number of articles, journals, countries/regions, institutions, authors, and keywords were assessed and visualized using CiteSpace software. RESULTS: The top 100 cited articles included 89 research papers and 11 reviews. The average total citation was 21. The most influential article with 146 citations was published by Dr. Liou E.J.W. in 2011. The most common level of evidence was level IV (36 articles). The Journal of Oral and Maxillofacial Surgery had the largest number of papers and the highest total citation frequency. The most productive countries and institutions were Korea/China and Chang Gung Memorial Hospital, respectively. Chen Yu-ray and Choi Jong Woo published 13 and 11 articles with 434 and 299 total citations, respectively. Research interests shifted from skeletal class III malocclusion, accuracy, stability, and relapse to quality of life and virtual surgical planning. CONCLUSION: Our bibliometric analyses provide a comprehensive landscape of the influential topics and developmental trends in surgery-first orthognathic surgery and inspire future studies in this booming field.