Prognostic value of 18F-FDG PET radiomics and sarcopenia in patients with oral squamous cell carcinoma.

BACKGROUND: Oral cancer is one of the most common malignancies in the head and neck region. Approximately 90% of oral cancers are oral squamous cell carcinomas (OSCC). 18F-FDG PET/CT has been used in OSCC patients for its high value in detecting metastatic lymph nodes and distant metastases. PET radiomics and sarcopenia can be measured on the PET and CT components of 18F-FDG PET/CT. PURPOSE: This study aimed to investigate the prognostic value of radiomics and sarcopenia measured on the PET and CT components of pre-operation 18F-FDG PET/CT in OSCC. METHODS: A total of 116 patients eventually enrolled in our study were randomly divided into two cohorts: training cohort (n = 58) and validation cohort (n = 58). The Cox model combined with the least absolute shrinkage and selection operator (LASSO) algorithm was applied to construct the radiomics score (Rad_score). The third lumber skeletal muscle index (L3 SMI) was calculated to identify sarcopenia. Univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factors. Based on the clinical factors, the clinical model was constructed, and the combined model was developed through the combination of the clinical model and Rad_score. C index, time-dependent C-index curves, receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis were used to evaluate the performance of prediction models. RESULTS: Three radiomics features constitute the Rad_score for overall survival (OS) and progression-free survival (PFS), respectively. Multivariate Cox regression analysis revealed that Rad_score was an independent prognostic factor, whereas sarcopenia was not. The combined models showed satisfactory performance in both the training cohort (C-index: OS:0.836, PFS:0.776) and the validation cohort (C-index: OS:0.744, PFS:0.712). The combined models were visualized as nomograms. Nomogram scores can realize the risk stratification of OSCC patients. Lower nomogram score is significantly related to the poorer OS (training cohort: p < 0.0001, validation cohort: p < 0.0001, overall cohort: p < 0.0001) and PFS (training cohort: p < 0.0001, validation cohort: p = 0.00017, overall cohort: p < 0.0001). CONCLUSIONS: Rad_score, but not sarcopenia, was an independent prognostic factor for patients with OSCC. The nomograms had a satisfactory performance, which might be helpful for OSCC patients and clinicians in personalized prognostic prediction and treatment decision-making.

Metabolism-Related Bioinformatics Analysis Reveals That HPRT1 Facilitates the Progression of Oral Squamous Cell Carcinoma In Vitro.

Objectives: Many studies have shown that dysregulation of metabolism contributes to oncogenesis. However, the exact roles of metabolism-related genes (MRGs) in oral squamous cell carcinoma (OSCC) remain unclear. Thus, we aimed to identify a prognostic signature related to MRGs in OSCC. Methods: The gene sequencing data of OSCC samples and the MRG set were downloaded from The Cancer Genome Atlas (TCGA) and the Molecular Signatures Database (MSigDB). The Wilcoxon rank-sum test was used to identify differentially expressed MRGs. Then, a prognostic signature was established by multivariate Cox regression analysis. Finally, prognosis-related MRGs were selected and further validated in OSCC tissues and cell lines. Results: A prognostic signature that included 8 MRGs was constructed. Multiple survival analysis revealed that only HPRT1 might be an independent biomarker and indicator of poor overall survival in OSCC patients. The expression of HPRT1 was then found to be upregulated in OSCC tissues and cell lines, and suppression of HPRT1 gene expression by siRNA inhibited the proliferation, migration, and invasion of OSCC cells in vitro. Conclusions: MRGs play an important role in the development of OSCC. Furthermore, HPRT1 might be an independent biomarker of OSCC and enhance OSCC proliferation, migration, and invasion in vitro; these results emphasize the potential utility of HPRT1 in OSCC therapy.

Bioinformatics Analyses Indicate That Cathepsin G (CTSG) is a Potential Immune-Related Biomarker in Oral Squamous Cell Carcinoma (OSCC).

PURPOSE: Plenty of studies showed that the immune system was associated with cancer initiation and progression. This study aimed to explore the prognostic biomarkers from immune-related genes (IRGs) in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) and IRGs and transcription factors (TFs) were extracted. Then, the co-expression network between IRGs and TFs was constructed using the "WGCNA" package in R software. Furthermore, a gene expression signature according to IRGs was constructed to predict OSCC prognosis and its accuracy was validated by survival analysis. Subsequently, correlation analyses between risk-score and immune cells level and clinical parameters were performed. Finally, immune-related biomarkers were selected and further investigated using gain-of-function assays in vitro. RESULTS: A total of 32 normal cases and 317 OSCC cases were selected in our study. Differentially-expressed analysis indicated that there were 381 differentially-expressed IRGs and 62 TFs in OSCC. Among them, 25 TFs and 21 IRGs were enrolled in the co-expression network. Furthermore, we found that gene expression signature on the basis of 10 IRGs could predict the prognosis accurately and a high-risk score based on gene expression signature meant a high T classification, terminal clinical stage, and low immune cells level in OSCC. Finally, cathepsin G (CTSG) was identified as a potential immune-related biomarker and therapeutic target in OSCC. CONCLUSION: In conclusion, IRGs were directly involved in the development and progression of OSCC. Furthermore, CTSG was identified as a potential independent biomarker and might be an immunotherapeutic target in OSCC treatment.

Piezoelectric properties of human dentin and some influencing factors.

OBJECTIVES: The present study focused on the piezoelectricity of human dentin. The effects of moisture content and orientation of tubules were investigated. METHODS: Fresh human dentin was cut with two surfaces generally parallel to the occlusal surface. The potentials generated by specimens were detected, as the compression loads were respectively parallel and vertical to the tubules. Moreover, specimens were dried and rehydrated; piezoelectric coefficients d(33) of dentin with different moisture content were measured horizontally to, and vertically to, the tubules. RESULTS: The results showed that piezoelectricity of dentin increased with increasing moisture content. Furthermore, greater piezoelectricity was detected parallel to the tubules than vertical to the tubules. SIGNIFICANCES: This study indicated that the piezoelectric properties of dentin were significantly affected by both humidity and orientation of the tubules. Both structural and free water in dentin is attributed to its piezoelectric properties.

DNetDB: The human disease network database based on dysfunctional regulation mechanism.

Disease similarity study provides new insights into disease taxonomy, pathogenesis, which plays a guiding role in diagnosis and treatment. The early studies were limited to estimate disease similarities based on clinical manifestations, disease-related genes, medical vocabulary concepts or registry data, which were inevitably biased to well-studied diseases and offered small chance of discovering novel findings in disease relationships. In other words, genome-scale expression data give us another angle to address this problem since simultaneous measurement of the expression of thousands of genes allows for the exploration of gene transcriptional regulation, which is believed to be crucial to biological functions. Although differential expression analysis based methods have the potential to explore new disease relationships, it is difficult to unravel the upstream dysregulation mechanisms of diseases. We therefore estimated disease similarities based on gene expression data by using differential coexpression analysis, a recently emerging method, which has been proved to be more potential to capture dysfunctional regulation mechanisms than differential expression analysis. A total of 1,326 disease relationships among 108 diseases were identified, and the relevant information constituted the human disease network database (DNetDB). Benefiting from the use of differential coexpression analysis, the potential common dysfunctional regulation mechanisms shared by disease pairs (i.e. disease relationships) were extracted and presented. Statistical indicators, common disease-related genes and drugs shared by disease pairs were also included in DNetDB. In total, 1,326 disease relationships among 108 diseases, 5,598 pathways, 7,357 disease-related genes and 342 disease drugs are recorded in DNetDB, among which 3,762 genes and 148 drugs are shared by at least two diseases. DNetDB is the first database focusing on disease similarity from the viewpoint of gene regulation mechanism. It provides an easy-to-use web interface to search and browse the disease relationships and thus helps to systematically investigate etiology and pathogenesis, perform drug repositioning, and design novel therapeutic interventions.Database URL: http://app.scbit.org/DNetDB/ #.

In situ study on the curing process of calcium phosphate bone cement.

The aim of this study was to follow the entire curing process of modified alpha-TCP cement, and to explore how the liquid phase affects the curing reaction. Two calcium phosphate bone cements (CPCs) with a variety of aqueous solution were studied for comparison. In situ X-ray diffraction analysis and pH testing were employed to follow the chemical reaction, while quantitative ultrasonic measurement (QUS) was carried out to monitor the physical change. Results showed that CPC powders were completely consumed after 72 h. Two steps were presented in apatite formation. The first step was the precipitation of carbonated hydroxyapatite (CHA), and in the second step, conversion of calcium deficient hydroxyapatite (CDHA) was the dominant reaction. Finally, CPCs were fully converted to apatite except the cement with NaH2PO4 as liquid phase, because acidic environment inhibited the conversion of apatite. The pH increased linearly after mixing, when supersaturation was reached, it decreased to pH approximately 6.0 gradually. Ultrasound measurement indicated that the variation of speed of sound (SOS) was related to both apatite formation and microstructural evolution. Ultrasonic attenuation coefficient (UAC) was able to quantitatively describe the curing process from viscous paste to elastic solid as a function of curing time. Moreover, the curing reaction conformed to classical dissolution-precipitation mechanism.