Objective: Oral squamous cell carcinoma (OSCC) is the most frequent oral malignancy with a poor prognosis, in which tumor-infiltrating immune cells may play a critical role. Therefore, our study aims to screen potential immune cells and immune-related genes for predicting OSCC prognosis. Methods: A total of 310 OSCC patients with full transcriptional data and clinical characteristics were extracted from the TCGA database. Then, we obtained their abundance of tumor-infiltrating immune cells on TIMER 2.0 and analyzed them using xCell method. Univariate and multivariate Cox regressions were applied successively to identify the immune cells associated with overall survival of OSCC patients. Furthermore, we screened the prognostic genes that related to the identified immune cells and validated their expressions by immunohistochemistry. Results: CD4⁺ central memory T (T_CM) cell was recognized as the sole independent immune cell correlated with OSCC prognosis (p = 0.0085). A novel nomogram based on CD4⁺ T_CM cell abundance was established for predicting the prognosis of OSCC patients, with calibration plots showing good performance for 1-, 3-, 5-year overall survival. Thirty-four related prognostic genes were screened according to the differential abundance of CD4⁺ T_CM cell infiltration. In immunohistochemistry analysis, DEFB1 showed a significant positive relationship with the density of CD4⁺ T_CM cells (p = 0.0075). Conclusion: CD4⁺ central memory T cell was proposed as an independent prognostic biomarker for OSCC patients. DEFB1 might positively regulate the abundance of tumor-infiltrating CD4⁺ T_CM cells, thus improving OSCC prognosis. Our findings may provide a new insight into better prognosis prediction and precise medicine for OSCC.

Background: Facial fracture is one of the most common injuries globally. Some types of facial fractures may cause irreversible damage and can be life-threatening. This study aimed to investigate the health burden of facial fractures at the global, regional, and national levels from 1990 to 2017. Methods: Facial fracture data, including the incidence, prevalence, and years lived with disability (YLDs) from 1990 to 2017, were obtained from the Global Burden of Disease study. We calculated the estimated annual percentage changes (EAPCs) to assess the changes of facial fractures in 195 countries or territories and 21 regions. Results: From 1990 to 2017, the change in cases of facial fracture incidence was 39% globally, while the age-standardized incidence rate showed a downtrend with an EAPC of 0.00. Syria experienced a ten-fold increase in incidence cases with an EAPC of 9.2, and this condition is largely responsible for the global health burden of facial fractures. The prevalence and YLDs showed a similar trend worldwide as the incidence. Additionally, we found that the incidence, prevalence, and YLDs showed a discrepancy among various age groups with a gradual change of proportion over the past 28 years. The age-standardized rates (ASRs) of facial fractures were nearly twice for male than those for female from 1990 to 2017. Conclusions: EAPC showed a correlation with the ASRs of facial fractures and had no relationship with socio-demographic index. The proportion of children and elderly suffering from facial fractures slightly changed with time. The ratio of facial fractures between males and females was 2:1. These findings suggest that more targeted and specific strategies based on age and gender should be established in various countries and regions.

A novel defined hypoxia-related gene signature to predict the prognosis of oral squamous cell carcinoma Ying Han, Xiaomeng Wang, Kun Xia, Tong Su

In South and Southeast Asian, the majority of buccal squamous cell carcinoma (BSCC) can arise from oral submucous fibrosis (OSF). BSCCs develop in OSF that are often not completely resected, causing local relapse. The aim of our study was to find candidate protein biomarkers to detect OSF and predict prognosis in BSCCs by quantitative proteomics approaches. We compared normal oral mucosa (NBM) and paired biopsies of BSCC and OSF by quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ) to discover proteins with differential expression. Gene Ontology and KEGG networks were analyzed. The prognostic value of biomarkers was evaluated in 94 BSCCs accompanied with OSF. Significant associations were assessed by Kaplan-Meier survival and Cox-proportional hazards analysis. In total 30 proteins were identified with significantly different expression (false discovery rate < 0.05) among three tissues. Two consistently upregulated proteins, ANXA4 and FLNA, were validated. The disease-free survival was negatively associated with the expression of ANXA4 (hazard ratio, 3.4; P = 0.000), FLNA (hazard ratio, 2.1; P = 0.000) and their combination (hazard ratio, 8.8; P = 0.002) in BSCCs. The present study indicates that iTRAQ quantitative proteomics analysis for tissues of BSCC and OSF is a reliable strategy. A significantly up-regulated ANXA4 and FLNA could be not only candidate biomarkers for BSCC prognosis but also potential targets for its therapy.