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1.
J Plast Reconstr Aesthet Surg ; 97: 33-40, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39128442

ABSTRACT

BACKGROUND: Segmental mandibulectomy and reconstruction of resulting defect can be performed via intraoral approach (IOA) or extraoral approach (EOA). Both approaches have advantages, disadvantages, indications, and contraindications to consider during their selection. OBJECTIVE: To compare IOA vs EOA of segmental mandibulectomy and microvascular reconstruction with fibula free flap (FFF). METHODS: We conducted a retrospective cohort study in which 51 patients who underwent segmental mandibulectomy and microvascular reconstruction with FFF from 2020 to 2024 were included, especially 17 patients by IOA and 34 patients by EOA, representing both groups of this study. Clinical characteristics, surgery parameters, and patients' prognosis were evaluated. Patients' satisfaction and Derriford Appearance Scale (DAS59) were assessed during follow-up. RESULTS: Ameloblastoma was the most frequent diagnosis (52.9% managed by IOA vs 70.6% by EOA); FFF was frequently positioned as double barrel (94.1% managed by IOA vs 88.2% by EOA). Compared with EOA group, IOA group had less intraoperative blood loss (mean difference [MD] = -112.2, 95% confidence interval [CI]: -178.9 to -45.5, p = 0.001), higher satisfaction score (MD = 1.3, 95% CI: 0.9 to 1.7, p ˂ 0.001), and lower DAS59 score (MD = -0.5, 95% CI: -0.7 to -0.2, p ˂ 0.001). CONCLUSION: Both IOA and EOA were found safe and feasible, presenting similar perioperative features and postoperative outcomes. Patients managed with IOA were more satisfied with aesthetic outcomes than patients managed with EOA. In the absence of simultaneous immediate implant during mandibular FFF reconstruction, after stability of FFF on the defect site, patients should always be referred to an implantologist and/or prosthodontist for teeth restoration to improve functional and aesthetic outcomes.


Subject(s)
Fibula , Free Tissue Flaps , Mandibular Osteotomy , Patient Satisfaction , Humans , Free Tissue Flaps/blood supply , Free Tissue Flaps/transplantation , Male , Female , Retrospective Studies , Mandibular Osteotomy/methods , Middle Aged , Fibula/transplantation , Fibula/blood supply , Adult , Plastic Surgery Procedures/methods , Mandibular Neoplasms/surgery , Aged , Ameloblastoma/surgery , Mandible/surgery , Mandibular Reconstruction/methods
2.
Sci Rep ; 14(1): 9824, 2024 04 29.
Article in English | MEDLINE | ID: mdl-38684755

ABSTRACT

PANoptosis plays a crucial role in cancer initiation and progression. However, the roles of PANoptosis-related genes (PARGs) in the prognosis and immune landscape of head and neck squamous cell carcinoma (HNSCC) remain unclear. Integrated bioinformatics analyses based on the data of HNSCC patients in the TCGA database were conducted. We extracted 48 PARGs expression profile and then conducted differentially expressed analysis, following building a Cox model to predict the survival of HNSCC patients. Subsequently, the relationships between the risk score, immune landscape, chemo-, and immune-therapy responses were analyzed, respectively. Moreover, we investigated the prognostic value, and further predicted the pathways influenced by PARGs. Finally, we identified the biological function of crucial PARGs. A total of 18 differentially expressed PARGs were identified in HNSCC, and a Cox model including CASP8, FADD, NLRP1, TNF, and ZBP1 was constructed, which showed that the risk score was associated with the prognosis as well as immune infiltration of HNSCC patients, and the risk score could be regarded as an independent biomarker. Additionally, patients with high-risk score might be an indicator of lymph node metastasis and advanced clinical stage. High-risk scores also contributed to the chemotherapy resistance and immune escape of HNSCC patients. In addition, FADD and ZBP1 played a crucial role in various cancer-related pathways, such as the MAPK, WNT, and MTOR signaling pathways. On the other hand, we suggested that FADD facilitated the progression and 5-fluorouracil (5-FU) resistance of HNSCC cells. A signature based on PANoptosis showed great predictive power for lymph node metastasis and advanced stage, suggesting that the risk score might be an independent prognostic biomarker for HNSCC. Meanwhile, FADD, identified as a prognostic biomarker, may represent an effective therapeutic target for HNSCC.


Subject(s)
Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms , Squamous Cell Carcinoma of Head and Neck , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/mortality , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Prognosis , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Female , Male , Computational Biology/methods , Gene Expression Profiling , Fas-Associated Death Domain Protein/metabolism , Fas-Associated Death Domain Protein/genetics , Lymphatic Metastasis
3.
Int J Mol Sci ; 24(3)2023 Jan 19.
Article in English | MEDLINE | ID: mdl-36768316

ABSTRACT

Increasing evidence suggests that aerobic glycolysis is related to the progression of oral squamous cell carcinoma (OSCC). Hence, we focused on glycolysis-related gene sets to screen for potential therapeutic targets for OSCC. The expression profiles of OSCC samples and normal controls were obtained from The Cancer Genome Atlas (TCGA). Then, the differentially expressed gene sets were selected from the official GSEA website following extraction of the differentially expressed core genes (DECGs). Subsequently, we tried to build a risk model on the basis of DECGs to predict the prognosis of OSCC patients via Cox regression analysis. Furthermore, crucial glycolysis-related genes were selected to explore their biological roles in OSCC. Two active glycolysis-related pathways were acquired and 66 DECGs were identified. Univariate Cox regression analysis showed that six genes, including HMMR, STC2, DDIT4, DEPDC1, SLC16A3, and AURKA, might be potential prognostic factors. Subsequently, a risk formula consisting of DEPDC1, DDIT4, and SLC16A3 was established on basis of the six molecules. Furthermore, DEPDC1 was proven to be related to advanced stage cancer and lymph node metastasis. Moreover, functional experiments suggested that DEPDC1 promoted the aerobic glycolysis, migration, and invasion of OSCC via the WNT/ß-catenin pathway. The risk score according to glycolysis-related gene expression might be an independent prognostic factor in OSCC. In addition, DEPDC1 was identified as playing a carcinogenic role in OSCC progression, suggesting that DEPDC1 might be a novel biomarker and therapeutic target for OSCC.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Squamous Cell Carcinoma of Head and Neck , Humans , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , GTPase-Activating Proteins/metabolism , Head and Neck Neoplasms/genetics , Mouth Neoplasms/pathology , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Squamous Cell Carcinoma of Head and Neck/genetics , Wnt Signaling Pathway/genetics
4.
Oral Dis ; 29(3): 923-932, 2023 Apr.
Article in English | MEDLINE | ID: mdl-34773352

ABSTRACT

OBJECTIVES: This study aimed to construct a formula to predict L3 skeletal muscle cross-sectional area (CSA) from C3 CSA and to select the cutoff values to evaluate the nutritional status in OSCC. MATERIALS AND METHODS: A total of 220 OSCC patients in Nanfang Hospital were divided into two groups: the training set (n = 100) and the validation set (n = 120). Patients in the training set were performed the preoperative whole-body positron emission tomography-computed tomography (PET/CT) scans, and patients in the validation set received preoperative head-and-neck computed tomography (CT) scans. C3 CSA and L3 CSA were delineated. The predictive formula was established, and the gender-specific thresholds of malnutrition were obtained by X-tile software in training set. Finally, the formula and cutoff values were validated. RESULTS: The predictive formula was successfully established. The gender-specific cutoff values for L3 SMI were 55.0 cm2 /m2 for men and 36.6 cm2 /m2 for women. There were no differences between the overall survival (OS) of patients diagnosed with malnutrition and that of patients who are not malnutrition. CONCLUSIONS: Our studies reveal that the L3 CSA could be calculated by C3 CSA conveniently with our formula in OSCC, which allowed us to assess malnutrition with head-and-neck CT image. However, there is no direct connection found between malnutrition and OS in OSCC. Hence, further studies with a larger sample size may be required.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Malnutrition , Mouth Neoplasms , Sarcopenia , Male , Humans , Female , Squamous Cell Carcinoma of Head and Neck/pathology , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Sarcopenia/diagnosis , Sarcopenia/pathology , Positron Emission Tomography Computed Tomography , Mouth Neoplasms/complications , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/pathology , Muscle, Skeletal/diagnostic imaging , Muscle, Skeletal/pathology , Prognosis , Malnutrition/etiology , Head and Neck Neoplasms/complications , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/pathology , Retrospective Studies
5.
Biomolecules ; 12(10)2022 Oct 12.
Article in English | MEDLINE | ID: mdl-36291667

ABSTRACT

Background: Head and neck squamous carcinoma (HNSC) poses a major threat to human life. The role of human papillomavirus (HPV) infection in the initiation and progression of HNSC is becoming more widely accepted. HPV-positive (HPV+) HNSC has shown unique responses to cancer therapies, which may be due to differences in immune cell infiltration. It is critical to determine how the immune responses to HPV in HNSC are regulated. Methods: Transcriptome data of HNSC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database were analyzed. Then, the CIBERSORT algorithm was used to calculate immune cell infiltration in HNSC. FDCSP expression level was detected by qPCR in the HNSC tissues collected from the Nanfang Hospital. Results: Follicular dendritic cell secreted protein (FDCSP) was highly expressed in HPV+ HNSC, and higher expression of FDSCP was associated with a favorable prognosis. In HPV+ HNSC samples, FDCSP significantly increased the proportion of T follicular helper cells (TFHs). FDCSP expression was also found to be associated with TP53 mutation status in HPV+ HNSC. The function of FDCSP was intimately connected to chemokine pathways, particularly with the C-X-C motif chemokine ligand 13 (CXCL13). We verified that the high expression of FDCSP in HPV+ HNSC and higher FDCSP is closely related to prognosis in HNSC samples we collected by qPCR. Conclusions: Collectively, these findings may provide fresh evidence that FDCSP is a potential chemokine-associated prognostic biomarker in HPV+ HNSC.


Subject(s)
Head and Neck Neoplasms , Papillomavirus Infections , Humans , Head and Neck Neoplasms/genetics , Papillomavirus Infections/genetics , Prognosis , Dendritic Cells, Follicular/metabolism , Ligands , Squamous Cell Carcinoma of Head and Neck/genetics , Biomarkers , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism
6.
J Oncol ; 2022: 7453185, 2022.
Article in English | MEDLINE | ID: mdl-35586208

ABSTRACT

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.

7.
Bioengineered ; 13(1): 496-507, 2022 01.
Article in English | MEDLINE | ID: mdl-34969361

ABSTRACT

Tumor-derived exosomes (exo) could modulate the biological behaviors of human umbilical vein endothelial cells (HUVECs). Here, the role of microRNA (miR)-10a-5p-modified gastric cancer (GC) cells-derived exo for HUVECs was studied. GC tissue specimens were collected, and miR-10a-5p and zinc finger MYND-type containing 11 (ZMYND11) levels were determined. HUVECs interfered with ZMYND11 or miR-10a-5p-related oligonucleotides. Exo was extracted from GC cells (HGC-27 exo), and miR-10a-5p mimic-modified HGC-27 exo were co-cultured with HUVECs. HUVECs viability, migration and angiogenesis were evaluated, and miR-10a-5p/ZMYND11 crosstalk was explored. It was observed that GC patients had raised miR-10a-5p and reduced ZMYND11, and miR-10a-5p negatively mediated ZMYND11 expression. Suppression of miR-10a-5p or overexpression of ZMYND11 inhibited viability, migration and tube formation ability of HUVECs. Notably, miR-10a-5p mimic-modified HGC-27 exo enhanced the viability, migration and tube formation ability of HUVECs, but this effect was impaired after up-regulating ZMYND11. In summary, miR-10a-5p from GC cells-derived exo enhances viability and migration of HUVECs by suppressing ZMYND11.


Subject(s)
Cell Cycle Proteins/genetics , Co-Repressor Proteins/genetics , DNA-Binding Proteins/genetics , Exosomes/genetics , MicroRNAs/genetics , Stomach Neoplasms/genetics , Cell Line, Tumor , Cell Movement , Cell Survival , Coculture Techniques , Gene Expression Regulation, Neoplastic , Human Umbilical Vein Endothelial Cells , Humans , Up-Regulation
8.
J Immunol Res ; 2021: 9250207, 2021.
Article in English | MEDLINE | ID: mdl-34950739

ABSTRACT

Increasing evidence indicated that the tumor microenvironment (TME) played a crucial role in cancer initiation and progression. Ubiquitin-conjugating enzyme E2C (UBE2C) was differentially expressed in many cancer types. However, the immunological and prognostic roles of UBE2C were unclear. Differentially expressed genes (DEGs) of 29 cancer types were downloaded from GEPIA2 and 4 cancer types failed to download owing to no DEGs. Furthermore, the gene expression profiles, mutation data, and survival data of 33 cancer types were obtained from UCSC Xena. Clinical stage relevance, tumor mutational burden (TMB), TME relevance analysis, and gene set enrichment analysis (GSEA) of DEGs in 33 cancer types were performed. And DEGs were identified in oral squamous cell carcinoma (OSCC) by biological experiments. Previous studies indicated that UBE2C was related to the prognosis of many cancers. In our study, the higher UBE2C expression level meant a terminal clinical stage in 8 cancer types and the expression level of UBE2C was related to TMB in 20 cancer types. In addition, both immune relevance analysis and GSEA showed that UBE2C might participate in immune response in many cancers. Furthermore, the UBE2C mRNA level and protein level were all identified as upregulated in OSCC cell lines and tissues. UBE2C was differentially expressed in many cancer types and related to the pathogenesis and TME of many cancers, which might be a potential diagnostic and therapeutic biomarker.


Subject(s)
Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Neoplasms/etiology , Tumor Microenvironment , Ubiquitin-Conjugating Enzymes/genetics , Adult , Aged , Computational Biology/methods , Disease Management , Disease Susceptibility , Female , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Neoplasms/diagnosis , Neoplasms/mortality , Neoplasms/therapy , Prognosis , Proportional Hazards Models , Protein Interaction Mapping , Transcriptome , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Ubiquitin-Conjugating Enzymes/metabolism
9.
J Cell Mol Med ; 25(9): 4444-4454, 2021 05.
Article in English | MEDLINE | ID: mdl-33837652

ABSTRACT

Increasing evidences have showed that autophagy played a significant role in oral squamous cell carcinoma (OSCC). Purpose of our study was to explore the prognostic value of autophagy-related genes (ATGs) and screen autophagy-related biomarkers for OSCC. RNA-seq and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database following extracting ATG expression profiles. Then, differentially expressed analysis was performed in R software and a risk score model according to ATGs was established. Moreover, comprehensive bioinformatics analyses were used to screen autophagy-related biomarkers which were later verified in OSCC tissues and cell lines. A total of 232 ATGs were extracted, and 37 genes were differentially expressed in OSCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these genes were mainly located in autophagosome membrane and associated with autophagy. Furthermore, the risk score on basis of ATGs was identified as potential independent prognostic biomarker. Moreover, ATG12 and BID were identified as potential autophagy-related biomarkers of OSCC. This study successfully constructed a risk model, and the risk score could predict the prognosis of OSCC patients accurately. Moreover, ATG12 and BID were identified as two potential independent prognostic autophagy-related biomarkers and might provide new OSCC therapeutic targets.


Subject(s)
Autophagy-Related Proteins/genetics , Autophagy , Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/pathology , Computational Biology/methods , Gene Expression Regulation, Neoplastic , Mouth Neoplasms/pathology , Apoptosis , Autophagy-Related Proteins/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Cell Proliferation , Female , Gene Expression Profiling , Gene Ontology , Gene Regulatory Networks , Humans , Middle Aged , Mouth Neoplasms/genetics , Mouth Neoplasms/metabolism , Prognosis , Survival Rate , Tumor Cells, Cultured
10.
Onco Targets Ther ; 14: 1275-1289, 2021.
Article in English | MEDLINE | ID: mdl-33658795

ABSTRACT

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.

11.
Cell Death Dis ; 11(12): 1055, 2020 12 12.
Article in English | MEDLINE | ID: mdl-33311454

ABSTRACT

Oral squamous cell carcinoma (OSCC) is the most common oral cancer. The molecular mechanisms of this disease are not fully understood. Our previous studies confirmed that dysregulated function of long non-coding RNA (lncRNA) AC007271.3 was associated with a poor prognosis and overexpression of AC007271.3 promoted cell proliferation, migration, invasion, and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. However, the underlying mechanisms of AC007271.3 dysregulation remained obscure. In this study, our investigation showed that AC007271.3 functioned as competing endogenous RNA by binding to miR-125b-2-3p and by destabilizing primary miR-125b-2, resulted in the upregulating expression of Slug, which is a direct target of miR-125b-2-3p. Slug also inhibited the expression of E-cadherin but N-cadherin, vimentin, and ß-catenin had no obvious change. The expression of AC007271.3 was promoted by the canonical nuclear factor-κB (NF-κB) pathway. Taken together, these results suggested that the classical NF-κB pathway-activated AC007271.3 regulates EMT by miR-125b-2-3p/Slug/E-cadherin axis to promote the development of OSCC, implicating it as a novel potential target for therapeutic intervention in this disease.


Subject(s)
Carcinogenesis/genetics , Carcinoma, Squamous Cell/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Mouth Neoplasms/genetics , NF-kappa B/metabolism , RNA, Long Noncoding/metabolism , Snail Family Transcription Factors/genetics , Animals , Base Sequence , Cell Line, Tumor , Cell Movement/genetics , Female , Gene Silencing , HEK293 Cells , Humans , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/metabolism , Neoplasm Invasiveness , Neoplasm Metastasis , RNA Stability/genetics , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Snail Family Transcription Factors/metabolism , Up-Regulation/genetics
12.
Aging (Albany NY) ; 12(12): 11667-11684, 2020 06 11.
Article in English | MEDLINE | ID: mdl-32526707

ABSTRACT

Increasing evidence suggests that N6-methyladenosine(m6A) has a vital role in cancer progression. Therefore, we aimed to explore the prognostic relevance of m6A-related genes in oral squamous cell carcinoma (OSCC). First, Expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and m6A-related genes were extracted afterwards. Then, cluster analysis and principal component analysis (PCA) were used to analyze m6A-related genes. And differentially-expressed analysis was performed in R software. Furthermore, a risk model was constructed, and crucial m6A genes were selected to explore its biological effects in OSCC cells. Total of 13 m6A-related genes were extracted and 8 differentially-expressed genes were identified. Subsequently, m6A-based clustering showed 2 subtypes with different clinical outcome. In addition, a risk model was successfully established. Of 13 m6A-related genes, only heterogeneous nuclear ribonucleoprotein C (HNRNPC) might be an independent biomarker and mean unfavorable overall survival in OSCC by univariate and multivariate cox regression analysis. Functional studies revealed that overexpression of HNRNPC promoted carcinogenesis of OSCC via epithelial- mesenchymal transition (EMT). In total, a risk model of m6A-related genes in OSCC was established. Subsequently, HNRNPC was proved to promote OSCC carcinogenesis and be an independent biomarker prognostic biomarker of OSCC, suggesting that it might be a new biomarker and therapeutic target of OSCC.


Subject(s)
Adenosine/analogs & derivatives , Biomarkers, Tumor/genetics , Heterogeneous-Nuclear Ribonucleoprotein Group C/genetics , Mouth Neoplasms/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Adenosine/metabolism , Biomarkers, Tumor/metabolism , Carcinogenesis/genetics , Cluster Analysis , Computational Biology , Datasets as Topic , Disease Progression , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic , Heterogeneous-Nuclear Ribonucleoprotein Group C/metabolism , Humans , Male , Methylation , Middle Aged , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Principal Component Analysis , Prognosis , RNA Processing, Post-Transcriptional , RNA, Messenger/metabolism , Risk Assessment , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/pathology
13.
Onco Targets Ther ; 13: 2599-2611, 2020.
Article in English | MEDLINE | ID: mdl-32273729

ABSTRACT

PURPOSE: Fibroblast activation protein (FAP) acts as a tumor promoter via epithelial-mesenchymal transition (EMT) in human oral squamous cell carcinoma (OSCC). The present study was designed to investigate the FAP targeting proteins and explore the precise mechanism by which FAP promotes EMT in OSCC. PATIENTS AND METHODS: Proteins interacting with FAP were found and filtered by immunoprecipitation-mass spectrometry (IP-MS). Both DPP9 protein and mRNA were examined in 90 paired OSCC samples and matched normal tissue. DPP9 knockdown was conducted to determine its function in OSCC in vitro and in vivo. RESULTS: Dipeptidyl peptidase 9 (DPP9) was identified as interacting with FAP intracellularly by IP-MS. The levels of both DPP9 protein and mRNA were down-regulated in OSCC tissue. Lower DPP9 expression was correlated with unfavorable survival rates of OSCC patients. DPP9 knockdown accelerates the proliferation of OSCC cells in vitro and in vivo. Overexpression of FAP leads to a reduction in DPP9 expression. Likewise, DPP9 overexpression reverses the proliferation, migration, invasion and EMT induced by FAP during OSCC. CONCLUSION: Our study finds that FAP promotes EMT of OSCC by down-regulating DPP9 in a non-enzymatic manner. FAP-DPP9 pathway could be a potential therapeutic target of OSCC.

14.
Life Sci ; 239: 117087, 2019 Dec 15.
Article in English | MEDLINE | ID: mdl-31759044

ABSTRACT

AIMS: Long noncoding RNA (lncRNA) AC007271.3 has been identified to be dysregulated in oral squamous cell carcinoma (OSCC) in our previous study. However, the precise role of AC007271.3 in OSCC remains unclear. In this study, we investigated the potential functions and the underlying mechanisms of AC007271.3 in OSCC. MATERIALS AND METHODS: The expression levels of AC007271.3 in OSCC tissues and cell lines were examined using RT-qPCR. The relationship between AC007271.3 level and clinicopathological characteristics was analyzed, and its association with patient prognosis was assessed by the Kaplan-Meier method. The biological function of AC007271.3 and its role in the development of OSCC through Wnt/ß-catenin signaling pathway were studied. KEY FINDINGS: We identified that AC007271.3 was up-regulated and positively correlated with advanced clinical stage, lymph node metastasis, poor histological differentiation and unfavorable prognosis. We explored the expression, function, and molecular mechanism of AC007271.3 in OSCC cells. Overexpression of AC007271.3 remarkably promoted cell proliferation in vitro and in vivo, induced cell migration, invasion and inhibited apoptosis in vitro, while knockdown of AC007271.3 attenuated cell proliferation, migration, invasion and induced apoptosis. Mechanistically, AC007271.3 overexpression substantially increased the expression of ß-catenin and the downstream target molecules CyclinD1, c-myc and Bcl-2, while silencing of AC007271.3 has the opposite effect. Rescued experiments showed that the ability to promote cell proliferation, migration, invasion and inhibiting apoptosis could be reversed when treated with the Wnt/ß-catenin pathway inhibitor. SIGNIFICANCE: Our data indicated that AC007271.3 could promote cell proliferation, invasion and inhibit cell apoptosis of OSCC via the Wnt/ß-catenin signaling pathway, which might provide a novel therapeutic approach for OSCC.


Subject(s)
Carcinoma, Squamous Cell/genetics , Mouth Neoplasms/genetics , RNA, Long Noncoding/genetics , Aged , Apoptosis/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , China , Female , Gene Expression Regulation, Neoplastic/genetics , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mouth Neoplasms/metabolism , Neoplasm Invasiveness/genetics , Prognosis , Signal Transduction/genetics , Wnt Signaling Pathway/genetics , Wnt Signaling Pathway/physiology , beta Catenin/genetics , beta Catenin/metabolism
15.
Front Oncol ; 9: 1054, 2019.
Article in English | MEDLINE | ID: mdl-31681590

ABSTRACT

Objectives: Oral squamous cell carcinoma (OSCC) is the most common oral cancer with a poor prognosis owing to limited understanding of the disease mechanisms. The aim of this study was to explore and identify the potential biomarkers in OSCC by integrated bioinformatics analysis. Materials and Methods: Expression profiles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were downloaded from The Cancer Genome Atlas (TCGA) and differentially expressed RNAs (DERNAs) were subsequently identified in OSCC by bioinformatics analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze DERNAs. Then, the competing endogenous RNA (ceRNA) network was constructed in Cytoscape and the protein -protein interaction (PPI) network was established in the STRING database. We established a risk model to predict the overall survival of OSCC on the basis of DElncRNAs with Kaplan-Meier analysis and combined with logrank p test. Furthermore, we identified potential biomarkers by combining univariate Cox regression with overall survival rate, which were then validated in Gene Expression Omnibus (GEO), OSCC cell lines and OSCC specimens. Results: A total of 1,919 DEmRNAs, 286 DElncRNAs and 111 DEmiRNAs were found to be dysregulated in OSCC. A ceRNA network included 46 DElncRNAs,7 DEmiRNAs and 10 DEmRNAs, and the PPI network included 712 DEmRNAs including 31 hub genes. Moreover, a 7 lncRNAs risk model was established and four genes (CMA1, GNA14, HCG22, HOTTIP) were identified as biomarkers on overall survival in patients with OSCC. Conclusions: This study successfully constructed a ceRNA network and a PPI network which play a crucial role in OSCC. A risk model was established to predict the prognosis, and four DERNAs are revealed with overall survival in patients with OSCC, suggesting that they may be potential biomarkers in tumor diagnosis and treatment.

16.
Forensic Sci Int ; 232(1-3): e12-23, 2013 Oct 10.
Article in English | MEDLINE | ID: mdl-24008199

ABSTRACT

Although exposure to animal venom and poison, such as snakebites, bee stings, and contact, with toads, is a common problem, reported deaths are rare. The present report discusses 18 fatal cases in China. Causes of death were grouped into 6 categories, including 1 case of tetrodotoxin poisoning, 1 case of gallbladder poisoning, 3 cases of snake venom toxicity, 4 cases of melittin toxicity, 4 cases of cantharidin poisoning and 5 cases of venenum bufonis poisoning. The epidemiology of each venom-induced death, the mechanism of exposure to venom, and the target organs and tissues affected by these toxic animals were here systematically reviewed. Such details are important to even suspected cases of venom damage. The associated problems related to forensic medicine, such as manner of death and possible attribution to the toxic effects of various animals, are also discussed herein.


Subject(s)
Poisoning/mortality , Abortifacient Agents/poisoning , Adolescent , Adult , Amphibian Venoms/poisoning , Animals , Bees , Bites and Stings/complications , Cantharidin/poisoning , Child , Child, Preschool , China , Female , Fishes , Forensic Toxicology , Gallbladder , Humans , Male , Melitten/poisoning , Middle Aged , Snake Bites/complications , Snake Venoms/poisoning , Tetraodontiformes , Tetrodotoxin/poisoning , Young Adult
17.
Fa Yi Xue Za Zhi ; 29(5): 333-6, 2013 Oct.
Article in Chinese | MEDLINE | ID: mdl-24466770

ABSTRACT

OBJECTIVE: To observe the pathological changes of major organs in rats with acute Dysosma versipellis poisoning and investigate the toxic mechanism and the injuries of target tissues and organs. METHODS: Forty Sprague-Dawley (SD) rats were randomly divided into three experimental groups, which were given the gavage with 0.5, 1.0 and 2.0 LDo doses of Dysosma versipellis decoction, and one control group, which was given the gavage with 1.0 LD0 dose of normal saline. The rats were sacrificed 14 days after Dysosma versipellis poisoning and samples including brain, heart, liver, lung, and kidney were taken. After pathological process, the pathological changes of the major organs and tissues were observed by light microscope and electron microscope. The experimental data were statistical analyzed by chi2 test. RESULTS: The observations of light microscopy: loose cytoplasm of neurons with loss of most Nissl bodies; swelling of myocardial cells with disappearance of intercalated disk and striations; hepatocellular edema with ballooning degeneration; and swelling epithelial cells of renal proximal convoluted tubule with red light coloring protein-like substances in the tube. The observations of electron microscopy: the structures of cell membrane and nuclear membrane of neurons were destroyed; cytoplasm of neurons, obvious edema; and most organelles, destroyed and disappeared. The mortalities of rats after acute poisoning of the four groups increased with doses (P < 0.05). CONCLUSION: Acute Dysosma versipellis poisoning can cause multi-organ pathological changes. There is a positive correlation between the toxic effect and the dosage. The target tissues and organs are brain (neurons), heart, liver and kidney.


Subject(s)
Berberidaceae/poisoning , Brain/pathology , Myocardium/pathology , Plant Extracts/poisoning , Animals , Berberidaceae/chemistry , Dose-Response Relationship, Drug , Female , Kidney/pathology , Liver/pathology , Male , Microscopy, Electron, Transmission , Neurons/drug effects , Neurons/pathology , Plant Extracts/administration & dosage , Random Allocation , Rats , Rats, Sprague-Dawley
18.
Fa Yi Xue Za Zhi ; 28(4): 252-5, 2012 Aug.
Article in Chinese | MEDLINE | ID: mdl-23033661

ABSTRACT

OBJECTIVE: To investigate Fas protein expression of the myocardium in dilated cardiomyopathy (DCM) and its relationship with occurrence of sudden death caused by DCM. METHODS: Nine autopsy cases of sudden death caused by DCM along with the heart samples were chosen from the archives in the Department of Forensic Medicine, Tongji Medical College, HUST from 1997 to 2007. Other 11 cases which died of violence and other diseases were selected as the control group. Expressions of myocardial Fas protein in the samples were quantitatively detected by immunohistochemistry and computerized imaging analysis. RESULTS: Myocardial Fas protein expression increased significantly in the DCM group. Positive color showed brown-yellow granulated or striped distribution in the longitudinal section of myocardial within the cell membrane and cytoplasm, and showed circular brown granules in the cross section of the cell membrane, while these changes were not observed in the control group though there was focal weak staining noted. Statistical significance was observed between the experimental and control groups (P = 0.002), but no statistical significance was found for the average optical density value between these two groups (P = 0.675). CONCLUSION: The expression of Fas protein increased obviously in the DCM group. Such alteration in expression quantity and distribution of myocardial Fas protein may be related to arrhythmia and heart failure in the patients with DCM.


Subject(s)
Cardiomyopathy, Dilated/metabolism , Death, Sudden, Cardiac/pathology , Myocardium/metabolism , fas Receptor/metabolism , Adult , Apoptosis , Autopsy , Cardiomyopathy, Dilated/pathology , Case-Control Studies , Death, Sudden, Cardiac/etiology , Female , Forensic Pathology , Humans , Immunohistochemistry , Male , Middle Aged , Myocardium/pathology , Young Adult , fas Receptor/genetics
19.
Am J Forensic Med Pathol ; 33(3): 273-5, 2012 Sep.
Article in English | MEDLINE | ID: mdl-21646904

ABSTRACT

We report a case of homicide due to intravenous mercury injection followed by meperidine and sodium cyanide injection. A 35-year-old woman was found dead in bed at home by her husband. Reportedly, she had been sick for more than 5 months. Initial death investigation revealed no evidence of foul play. Her death was believed to be natural. Therefore, her body was buried without an autopsy. Two months after death, her family requested an autopsy because they suspected her physician husband killed her. Her body was exhumed, and an autopsy was performed. Postmortem examination revealed numerous metallic mercury globules in the pulmonary arteries. Toxicological analysis revealed a high concentration of mercury in the tissue samples of the lungs, liver, heart, and kidney. In addition, cyanide and meperidine were also found in the heart and liver. The detailed case history and postmortem examination findings are described.


Subject(s)
Homicide , Meperidine/poisoning , Mercury Poisoning/diagnosis , Narcotics/poisoning , Sodium Cyanide/poisoning , Adult , Exhumation , Female , Forensic Pathology , Forensic Toxicology , Humans , Injections, Intravenous , Kidney/chemistry , Kidney/pathology , Liver/chemistry , Liver/pathology , Lung/chemistry , Lung/pathology , Male , Meperidine/administration & dosage , Meperidine/analysis , Mercury/administration & dosage , Mercury/analysis , Myocardium/chemistry , Myocardium/pathology , Narcotics/administration & dosage , Narcotics/analysis , Poisons/administration & dosage , Poisons/analysis , Pulmonary Artery/chemistry , Pulmonary Artery/pathology , Sodium Cyanide/administration & dosage , Sodium Cyanide/analysis
20.
Fa Yi Xue Za Zhi ; 27(3): 200-4, 2011 Jun.
Article in Chinese | MEDLINE | ID: mdl-21899012

ABSTRACT

OBJECTIVE: To provide references for forensic expertise by investigating the kinds of toxicant, routes of exposure and manners of poisoning deaths, etc. METHODS: Six hundred and seven autopsy cases of poisoning deaths from 1957 to 2008 in Department of Forensic Medicine, Tongji Medical College (Tongji Forensic Science Identification Center of Hubei), were comparatively reviewed. RESULTS: In 218 cases from 1999 to 2008, more than 50% of decedents were male in the ages of 30-49. The toxicants are usually taken orally and the most common manner of death was accidental. The common substances involved in poisoning death were rodenticide, poisoning gas and insecticide. Compared to the data of 1983-1998 and 1957-1982, the common toxic agents had changed significantly. The number of cases involving insecticide and cyanide poisoning decreased in recent years, and the number of cases of rodenticide, poisoning gas, alcohols poisoning displayed an increase tendency, especially for drugs abuse. CONCLUSION: Poisoning deaths of pesticides remain a major public health problem for a long time and the awareness of prevention need to be raised, especially for the prevention of deaths from multiple poisons.


Subject(s)
Accidents/statistics & numerical data , Alcoholic Intoxication/epidemiology , Pesticides/poisoning , Poisoning/epidemiology , Adolescent , Adult , Age Distribution , Aged , Anesthetics/poisoning , Autopsy , Carbon Monoxide Poisoning/epidemiology , Cause of Death , Child , Child, Preschool , China/epidemiology , Female , Forensic Medicine , Heroin/poisoning , Humans , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/poisoning , Infant , Male , Middle Aged , Poisoning/etiology , Retrospective Studies , Rodenticides/poisoning , Sex Distribution , Suicide/statistics & numerical data , Young Adult
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