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Interleukin-1 receptor antagonist (IL-1RA) has been shown to play an important role in cancer progression. However, its pathogenic effects and molecular mechanism in the malignant progression of esophageal squamous cell carcinoma (ESCC) remain largely unknown. This study was designed to explore the function of IL-1RA in ESCC and determine the relationship between IL-1RA and lymph node metastasis in ESCC patients. The clinical relevance of IL-1RA in relation to the clinicopathological features and prognosis of 100 ESCC patients was analyzed. The function and underlying mechanisms of IL-1RA in the growth, invasion, and lymphatic metastasis in ESCC were explored both in vitro and in vivo. The therapeutic effect of anakinra, an IL-1 receptor antagonist, on ESCC was also evaluated in animal experiments. Downregulation of IL-1RA was observed in ESCC tissues and cells and was found to be strongly correlated with pathological stage (P = 0.034) and lymphatic metastasis (P = 0.038). Functional assays demonstrated that upregulation of IL-1RA reduced cell proliferation, migration, and lymphangiogenesis both in vitro and in vivo. Mechanistic studies revealed that overexpression of IL-1RA activated the epithelial-to-mesenchymal transition (EMT) in the ESCC cells through activation of MMP9 and regulation of the expression and secretion of VEGF-C through the PI3K/NF-κB pathway. Anakinra treatment resulted in significant inhibition of tumor growth, lymphangiogenesis, and metastasis. IL-1RA inhibits lymph node metastasis of ESCC by regulating the EMT through activation of matrix metalloproteinase 9(MMP9) and lymphangiogenesis, driven by VEGF-C and the NF-κB signaling pathway. Anakinra may be an effective drug for the inhibition of ESCC tumor formation and lymph node metastasis.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteína Antagonista do Receptor de Interleucina 1/genética , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Linfangiogênese/genética , Metástase Linfática , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , NF-kappa B/genética , Fator C de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: This study aimed to investigate the safety and efficacy of minimally invasive total mesoesophageal excision (TME) for esophageal cancer. METHODS: We retrospectively collected data from patients with esophageal cancer who underwent esophagectomy at our center between January 2011 and June 2017. Among 611 eligible patients, 302 underwent minimally invasive total mesoesophageal excision (the TME group) and 309 underwent non-total mesoesophageal excision (the NME group). Outcomes were compared after 1-to-1 propensity score matching, and subgroup analyses were performed for cases involving pT1-2 or pT3-4a disease. RESULTS: The propensity score matching produced 249 pairs of patients. The TME group had a shorter operative time (P < 0.001), lower intraoperative bleeding (P < 0.001), and a shorter postoperative hospital stay (P < 0.001). There were no significant differences between the two groups in the number of removed lymph nodes, 30-day mortality, or postoperative complications. In addition, both groups had similar 3-year rates of overall survival (OS) and disease-free survival (DFS). However, the 3-year recurrence rate in the esophageal bed was significantly lower in the TME group (P = 0.033). Furthermore, among patients with pT3-4a disease, the TME group had better 3-year rates of OS, DFS, and recurrence. CONCLUSION: Minimally invasive total mesoesophageal excision appears to be a safe technique that can reduce tumor recurrence in the esophageal bed. Furthermore, this technique provided survival benefits for patients with pT3-4a disease.
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Neoplasias Esofágicas , Laparoscopia , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Humanos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Leucine-rich repeat-coupled receptor 6 (LGR6) is a marker of the skin, nails, and other types of adult tissue stem cells and has been widely found to be related to the development and progression of a variety of cancer types. The clinical significance and biological function of LGR6 in esophageal squamous cell carcinoma (ESCC) have not been determined. METHODS: The expression of LGR6 at the transcriptional level was analyzed by searching the TCGA and UCSC data sets. Immunohistochemistry, WB, and q-PCR were used to detect the expression of LGR6 in ESCC and adjacent normal tissues. LGR6 PPI networks and KEGG pathways were used to analyze the potential biological functions of LGR6. RESULTS: The expression of LGR6 in ESCC tissues was significantly higher than that in normal tissues and was negatively correlated with the differentiation degree of ESCC and the prognosis of the patients but not closely correlated with the TNM stage of ESCC. PPI networks showed that LGR6 had a close interaction with RSPO1, RSPO2, RSPO3, and RSPO4. KEGG pathway analysis showed that LGR6 activated the Wnt/ß-catenin signaling pathway by binding with RSPO ligands to promote the progression of ESCC. CONCLUSION: LGR6 can serve as a potential diagnostic and prognostic marker for ESCC.
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Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Idoso , Biomarcadores Tumorais/genética , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Mapas de Interação de Proteínas , Trombospondinas/metabolismoRESUMO
BACKGROUND: Interleukin-1 promotes tumor angiogenesis through VEGF production. The interleukin-1 receptor antagonist can suppress tumors by blocking this effect. METHODS: Immunohistochemistry, WB, and gene sequencing were used to analyze the expression of IL-1RA in esophageal cancer patients. WB was used to detect the expression of IL-1RA and interleukin-1α in esophageal cancer cells. Stable ESCC cell models overexpressing the IL-1RA were constructed. Their cell functions were tested, and their effects on VEGF were examined. RESULTS: IL-1RA is downregulated in primary EC tumors, and this downregulation of IL-1RA is closely related to TNM staging and survival prognosis. The overexpression of IL-1RA increased the proliferation of KYSE410 EC cells, which have a high level of IL-1α expression. Overexpression of IL-1RA in KYSE410 cells promotes a decrease in the expression of VEGF-A. However, IL-1RA expression did not cause any changes in EC9706 cells with low IL-1α expression. CONCLUSION: IL-1RA acts as a tumor suppressor, and its deletion promotes tumor progression by increasing VEGF-A expression in ESCC.
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Neoplasias Esofágicas/patologia , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1alfa/metabolismo , Idoso , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1alfa/genética , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
This study aimed to investigate the incidence and risk factors of deep surgical site infection (DSSI) during hospitalisation after closed tibial plateau fractures treated with open reduction and internal fixation (ORIF). We performed this retrospective study at a university-affiliated hospital with an advanced trauma centre. The data of adult patients with closed tibial plateau fractures treated with ORIF from January 2012 to February 2017 were extracted from the electronic medical records. Demographics, injury-related and surgery-related variables of DSSI and non-DSSI groups were compared by univariate test. Multivariate logistic analysis models were used to investigate the independent risk factors. In total, 676 patients with complete data met the inclusion criteria and were included, and of them, 17 developed DSSI (2.51%) during hospitalisation. Approximately 60% (9/17) of DSSI was caused by Staphylococcus aureus. Compared to the non-DSSI group, DSSI patients had a significantly longer stay in hospital (25.8 vs 15.2 days). Independent risk factors of DSSI identified by multivariate analysis were higher BMI (>26.0) (OR, 1.58; 95% CI, 1.09 to 3.27; P = 0.032), prolonged surgical duration (>138 min) (OR, 4.26; 95% CI, 1.54 to 11.19; P = 0.005) and current smoking (OR, 3.42; 95% CI, 1.47 to 8.62; P = 0.01). A relatively low incidence rate of DSSI (2.51%) was found in this study, and several significant risk factors were identified. Smoking cessation programmes should be implemented immediately after hospitalisation, especially for obesity and morbid obesity patients. Detailed and comprehensive preoperative assessment and a considerate operative plan should be guaranteed to reduce surgical duration.
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Fixação Interna de Fraturas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Infecção da Ferida Cirúrgica/etiologia , Fraturas da Tíbia/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
Esophageal cancer, ranked as the seventh most common cancer globally, encompasses squamous cell carcinoma and adenocarcinoma. Despite advancements in treatment modalities like surgery, chemotherapy, radiotherapy, and immunotherapy, radiotherapy, while crucial for enhancing local control and survival, poses risks for long-term side effects and the development of second primary malignancies (SPM), notably Second primary lung cancer (SPLC). This study aims to analyze the incidence of second primary lung cancer (SPLC) among esophageal cancer survivors, with a focus on the influence of radiotherapy, analyze variations across different demographic and clinical subgroups, and assess patient survival outcomes. Using data from the Surveillance, epidemiology, and end results (SEER) program on 56,493 esophageal cancer patients (2000-2020), we compared SPLC incidence in those with and without prior radiotherapy. We applied a competing risks framework, propensity score matching (PSM), and survival analyses to assess SPLC risk and radiotherapy's impact. The study showed that patients treated with radiotherapy have a significantly higher long-term risk of SPLC compared to those without it. Radiotherapy significantly raised SPLC risk (HR 1.41, 95% CI 1.06-1.88), with higher SIRs particularly in younger patients and females. Post-PSM, there were significant differences in cancer-specific survival between esophageal cancer survivors with post-radiotherapy SPLC and those with only primary lung cancer. This cohort study shows that radiotherapy in esophageal cancer survivors increases SPLC risk but does not worsen survival compared to those with OPLC, highlighting the need for long-term monitoring and management.
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Sobreviventes de Câncer , Neoplasias Esofágicas , Neoplasias Pulmonares , Segunda Neoplasia Primária , Programa de SEER , Humanos , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/mortalidade , Feminino , Masculino , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/epidemiologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/epidemiologia , Pessoa de Meia-Idade , Idoso , Sobreviventes de Câncer/estatística & dados numéricos , Incidência , Radioterapia/efeitos adversos , Análise de SobrevidaRESUMO
PURPOSES: To investigate the features of the anterior segment structures in neovascular glaucoma (NVG) and analyze its differences from primary angle-closure glaucoma (PACG). METHODS: This study included patients who were first diagnosed with monocular NVG and PACG at the Affiliated Eye Hospital of Nanchang University during August 2019 to June 2022. Ultrasound biomicroscopy (UBM) was used to measure the anterior segment parameters of those eyes, including anterior chamber depth (ACD), anterior chamber width (ACW), anterior chamber area (ACA), iris area (IA), maximum iris thickness (ITMAX), middle iris thickness (ITMID), iris curvature (IC), lens vault (LV), angle opening distance (AOD500), trabecular iris angle (TIA500), trabecular-iris space area (TISA500) and peripheral anterior synechia (PAS) length. RESULTS: In this study, paired samples t-test showed that IA [1.170(0.324) mm2], ITMAX [0.368(0.079) mm], ITMID [0.280(0.062) mm] and IC [0.147(0.037) mm] of NVG were smaller than F-NVG [2.058(0.195) mm2, 0.611(0.045) mm, 0.415(0.049) mm and 0.272(0.077) mm], the AOD500, TIA500, and TISA500 of NVG were also smaller than F-NVG. Independent samples t-test showed that ACD [2.349(0.350) mm] and ACA [16.326(3.547) mm2] of NVG were larger than PACG [1.971(0.240) mm, 12.030(1.860) mm2], but the IA [1.170(0.324) mm2], ITMAX [0.368(0.079) mm], ITMID [0.280(0.062) mm], IC [0.147(0.037) mm] and LV [0.436(0.172 mm)] were smaller than PACG [1.740(0.294) mm2, 0.548(0.084) mm, 0.404(0.065) mm, 0.283(0.060) mm and 0.737(0.196) mm]. Among the 16 patients with 360° angle-closure NVG, the PAS length was 0.834 (0.326) mm, which exceeded the Schwalbe line. CONCLUSION: In NVG, the iris is atrophied, thinned, and straight, while the ACD is normal or slightly shallow. In 360° angle-closure NVG, the PAS length exceeds the Schwalbe line, presenting a pseudo angle phenomenon and a hockey stick sign. Notably, the anterior segment structure morphology of NVG exhibit differences from those of PACG.
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Lung cancer, a global mortality leader, often necessitates Video-Assisted Thoracoscopic (VATS) surgery. However, post-operative nausea and vomiting (PONV) is common, highlighting a need for effective management and prevention strategies in this context. A retrospective case-control study at Fujian Medical University Union Hospital evaluated patients undergoing VATS radical resection of lung cancer between May and September 2022. Patients were categorized based on PONV prevention methods, and data encompassing demographics, surgical history, and postoperative adverse events s were analyzed to assess the association between prophylactic protocols and PONV incidence. The Netupitant and Palonosetron Hydrochloride (NEPA) group showed a significant reduction in PONV occurrences post-surgery compared to Ondansetron (ONDA) and Control groups, emphasizing NEPA's efficacy in alleviating PONV symptoms (P < 0.05). Furthermore, following VATS radical resection of lung cancer, NEPA markedly reduced the intensity of PONV symptoms in patients. Both univariate and multivariate logistic analyses corroborated that NEPA independently reduces PONV risk, with its protective effect also apparent in susceptible populations like females and non-smokers. NEPA utilization markedly reduced both the incidence and severity of PONV in patients undergoing VATS radical resection of lung cancer, serving as an independent protective factor in mitigating PONV risk post-surgery.
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Neoplasias Pulmonares , Náusea e Vômito Pós-Operatórios , Cirurgia Torácica Vídeoassistida , Humanos , Feminino , Cirurgia Torácica Vídeoassistida/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Masculino , Neoplasias Pulmonares/cirurgia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Náusea e Vômito Pós-Operatórios/etiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Estudos de Casos e Controles , Antieméticos/uso terapêutico , Antieméticos/administração & dosagem , Ondansetron/uso terapêutico , Ondansetron/administração & dosagem , Palonossetrom/uso terapêutico , Palonossetrom/administração & dosagemRESUMO
Background: Lung cancer is the most common global cancer in terms of incidence and mortality. Its main driver is tobacco smoking. The identification of modifiable risk factors isa public health priority. Green tea consumption has been examined in epidemiological studies, with inconsistent findings. Thus, we aimed to apply Mendelian randomization to clarify any causal link between green tea consumption and the risk of lung cancer. Methods: We utilized a two-sample Mendelian randomization (MR) approach. Genetic variants served as instrumental variables. The goal was to explore a causal link between green tea consumption and different lung cancer types. Green tea consumption data was sourced from the UK Biobank dataset, and the genetic association data for various types of lung cancer were sourced from multiple databases. Our analysis included primary inverse-variance weighted (IVW) analyses and various sensitivity test. Results: No significant associations were found between green tea intake and any lung cancer subtypes, including non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma) and small cell lung cancer. These findings were consistent when applying multiple Mendelian randomization methods. Conclusion: Green tea does not appear to offer protective benefits against lung cancer at a population level. However, lung cancer's complex etiology and green tea's potential health benefitssuggest more research is needed. Further studies should include diverse populations, improved exposure measurements and randomized controlled trials, are warranted.
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Objective: To explore the application value of adjustable skin stretchers for repairing skin wound defects. Methods: Twenty patients with skin defects were included in this study. The largest defect was measured to be 45.4 cm × 13.3 cm (length × width) and the smallest one was 4.4 cm × 3.2 cm (length × width). All patients were subjected to adjustable skin stretchers and the short- and long-term clinical efficacy was evaluated. Results: The wounds of all enrolled patients were healed completely except for one patient with a dorsal foot infection (the patient requested to return to the local county hospital for further treatment), with a total satisfaction of 100%. Postoperative 3-month follow-up showed scar formation, a little local hyperpigmentation, normal skin elasticity, and intact organs of involved cases, thus signifying the significant impact of adjacent joint activities. Conclusion: Adjustable skin stretchers can accurately control the tension on wound margins, breaking the limitation of previous stretchers to provide objective quantitative indicators for clinical application. These stretchers are characterized by high use-value and are worth promoting.
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The objective of this study is to evaluate the efficacy of deep learning (DL) techniques in improving the quality of diffusion MRI (dMRI) data in clinical applications. The study aims to determine whether the use of artificial intelligence (AI) methods in medical images may result in the loss of critical clinical information and/or the appearance of false information. To assess this, the focus was on the angular resolution of dMRI and a clinical trial was conducted on migraine, specifically between episodic and chronic migraine patients. The number of gradient directions had an impact on white matter analysis results, with statistically significant differences between groups being drastically reduced when using 21 gradient directions instead of the original 61. Fourteen teams from different institutions were tasked to use DL to enhance three diffusion metrics (FA, AD and MD) calculated from data acquired with 21 gradient directions and a b-value of 1000 s/mm2. The goal was to produce results that were comparable to those calculated from 61 gradient directions. The results were evaluated using both standard image quality metrics and Tract-Based Spatial Statistics (TBSS) to compare episodic and chronic migraine patients. The study results suggest that while most DL techniques improved the ability to detect statistical differences between groups, they also led to an increase in false positive. The results showed that there was a constant growth rate of false positives linearly proportional to the new true positives, which highlights the risk of generalization of AI-based tasks when assessing diverse clinical cohorts and training using data from a single group. The methods also showed divergent performance when replicating the original distribution of the data and some exhibited significant bias. In conclusion, extreme caution should be exercised when using AI methods for harmonization or synthesis in clinical studies when processing heterogeneous data in clinical studies, as important information may be altered, even when global metrics such as structural similarity or peak signal-to-noise ratio appear to suggest otherwise.
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Aprendizado Profundo , Transtornos de Enxaqueca , Humanos , Imagem de Tensor de Difusão/métodos , Inteligência Artificial , Imagem de Difusão por Ressonância Magnética/métodos , Transtornos de Enxaqueca/diagnóstico por imagem , Encéfalo/diagnóstico por imagemRESUMO
Objective: Neoadjuvant chemoradiotherapy (nCRT) plays an important role in patients with locally advanced esophageal cancer (EC). We aim to determine the prognostic risk factors and establish a reliable nomogram to predict overall survival (OS) based on SEER population. Methods: Patients with EC coded by 04-15 in the SEER database were included. The data were divided into training group and verification group (7:3). The Cox proportional-risk model was evaluated by using the working characteristic curve (receiver operating characteristic curve, ROC) and the area under the curve (AUC), and a nomogram was constructed. The calibration curve was used to measure the consistency between the predicted and the actual results. Decision curve analysis (DCA) was used to evaluate its clinical value. The best cut-off value of nomogram score in OS was determined by using X-tile software, and the patients were divided into low-risk, medium-risk, and high-risk groups. Results: A total of 2,209 EC patients who underwent nCRT were included in further analysis, including 1,549 in the training cohort and 660 in the validation group. By Cox analysis, sex, marital status, T stage, N stage, M stage, and pathological grade were identified as risk factors. A nomogram survival prediction model was established to predict the 36-, 60-, and 84-month survival. The ROC curve and AUC showed that the model had good discrimination ability. The correction curve was in good agreement with the prediction results. DCA further proved the effective clinical value of the nomogram model. The results of X-tile analysis showed that the long-term prognosis of patients in the low-risk subgroup was better in the training cohort and the validation cohort (p < 0.001). Conclusion: This study established an easy-to-use nomogram risk prediction model consisting of independent prognostic factors in EC patients receiving nCRT, helping to stratify risk, identify high-risk patients, and provide personalized treatment options.
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Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal and aggressive tumor. Our previous study revealed that tropomyosin 3 (TPM3) is up-regulated in the late stage of ESCC and promotes epithelial-mesenchymal transition (EMT) via MMP2/MMP9. However, we have not yet explored the upstream regulator of TPM3. In this study, miR-107, a microRNA molecule, was predicted as an inhibitor targeting TPM3, and in vivo and in vitro experiments confirmed this hypothesis. Methods: Western blot and fluorescence quantitative polymerase chain reaction (qPCR) were applied to analyze the expression of miR-107 and TPM3. Flow cytometry, cell counting kit-8 (CCK8) assay, wound-healing assay, colony formation assay, transwell assay, and a BALB/c nude mouse (male, 8 weeks old, 20±2 g) model were used to detect the function of miR-107 and TPM3 in ESCC. Dual-luciferase assay was used to analyze the suppressed TPM3 expression induced by miR-107. Rescue experiments were also conducted in our research. Results: The cell and nude mouse models verified that TPM3 promotes proliferation, invasion and metastasis, and inhibits apoptosis, which is the opposite effect of miR-107 in ESCC. Meanwhile, the expression of TPM3 was up-regulated in the ESCC sample and cell lines, and miR-107 was down-regulated correspondingly. Dual-luciferase detection confirmed that miR-107 decreased the expression of TPM3 by targeting the 3'-untranslated region (3'-UTR) at the end of the TPM3 transcript. Further experiments verified that TPM3 could rescue the tumor suppression effect derived from miR-107. Conclusions: MiR-107 negatively regulates TPM3 expression and plays a tumor suppression role in ESCC.
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Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignant tumors worldwide, and a larger number of ESCC patients have unsatisfactory overall survival (OS) rates. While pyroptosis participates in the development of a variety of malignancies, the function of pyroptosis-related genes (PRGs) in ESCC is still obscure. The aim of this study was to construct the pyroptosis-related prognostic model for ESCC, which will be developed to stratify the risk hazards of ESCC patients and to provide theoretical evidence for individualized treatment. Methods: RNA-seq data of ESCC were download from the NCBI Gene Expression Omnibus (GEO) database. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to explore the potential biological functions or pathways. OS was considered as the primary prognosis outcome in this study. The riskscore was constructed by Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis. The pyroptosis-related prognostic model was constructed based on all independent prognostic factors and verified by C-index, Receiver operating characteristic (ROC) curves, and Calibration curves, and the role of the riskscore in ESCC immunotherapy was evaluated by the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Results: The current study found 31 differentially expressed PRGs (P<0.001), and functional enrichment analysis showed these PRGs were enriched in positive regulation of cytokine production, interleukin-1 beta production. Univariate and multivariate Cox regression analysis were applied to validate that the riskscore based on four prognostic PRGs (HMGB1, IL-18, NLRP7, and PLCG1) was an independent prognostic factor for ESCC, and the C-index of prognostic model related to the riskscore (C-index =0.705) was higher than that of tumor node metastasis (TNM) stage (0.620). The low-risk group showed a better efficacy of immune checkpoint inhibitors. Conclusions: The riskscore related to PRGs was one of the independent prognostic factors for ESCC. Moreover, the prognostic model related to the riskscore could be used to predict the OS of ESCC patients effectively. However, there still were several limitations in this study, such as no external validation sample. In summary, our data provides a novel perspective in exploring the potential prognostic biomarkers of ESCC.
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Increasing evidence has indicated that long non-coding RNAs (LncRNAs) play multiple functions in the development of cancer and function as indicators of diagnosis and prognosis. This aim of this study was to investigate the roles LncRNA C9orF139 had in the progression of esophageal squamous carcinoma (ESCC). We found C9orf139 was highly expressed in ESCC and knock down the expression of C9orf139 significantly suppressed cell proliferation, promoted apoptosis, and inhibited migration and invasion. C9orf139 was able to negatively regulate miR-661 expression. At the same time, HDAC11 expression was negatively regulated by miR-661. The C9orf139/miR-661/HDAC11 axis was further involved in regulating the expression of the NF-κB signaling pathway. The association between the C9orf139 knockdown and the reduced tumor growth and size was observed during in vivo study. C9orf139 is highly expressed in ESCC, and is thus qualified to be used as a potential diagnostic and prognostic marker for ESCC. Its promotion of ESCC progression is achieved by mediating the miR-661/HDAC11 axis.
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BACKGROUND: With advances in thoracoscopic surgical instruments and techniques, subxiphoid video-assisted thoracic surgery (S-VATS) has become the main approach for anterior mediastinal tumor resection under thoracoscopy. However, the drawbacks of S-VATS, including it being a relatively unfixed surgical procedure, make it complicated and difficult for unexperienced surgeons to master. METHODS: This study retrospectively reviewed and analyzed consecutive patients with anterior mediastinal tumor or myasthenia gravis (MG) who underwent S-VATS at the Fujian Medical University Union Hospital, China, between March 2015 and April 2019.Patients were divided into the conventional group and the "four-zone one-way" group. Intraoperative and postoperative variables were compared between the groups. Cumulative sum (CUSUM) analysis was applied to determine the operation time (OT)-learning curve of the S-VATS "four-zone one-way" method. RESULTS: A total of 82 patients were included in this analysis, of which, 40 patients underwent the conventional method of S-VATS and 42 patients underwent the "four-zone one-way" method. Patients in the "four-zone one-way" group had significantly shorter OT (138.50±29.43 and 118.00±28.18 minutes, respectively; P=0.002) and significantly less blood loss (36.00±20.16 and 23.92±14.96 mL, respectively; P=0.003) compared with patients in the conventional group. Our data indicated that there was no difference of the efficacy of MG treatment between the 2 groups. The difference in the preoperative and postoperative quantitative MG scoring system score (QMG-score) and the dose reduction of cholinesterase inhibitors was comparable between patients in the 2 groups. According to the CUSUM analysis curve, after a steady improvement over phase I (cases 1-12 for the traditional method and cases 1-5 for the "four-zone one-way" method), the surgical procedure could be mastered. Phase III occurred after case 26 in the traditional group and case 28 in the "four-zone one-way" group, and is characterized by rapid improvements. CONCLUSIONS: Compared with the conventional method of S-VATS, the "four-zone one-way" method significantly decreased OT and estimated blood loss. These results demonstrated the feasibility and safety of the "four-zone one-way" method of S-VATS.
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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common human malignancy worldwide. The tumorigenesis mechanism in ESCC is unclear. MATERIALS AND METHODS: To explore potential therapeutic targets for ESCC, we analyzed 3 microarray datasets (GSE20347, GSE38129, and GSE67269) derived from the gene expression omnibus (GEO) database. Then, the GEO2R tool was used to screen out differently expressed genes (DEGs) between ESCC and normal tissue. Gene ontology function and kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using the database for annotation, visualization and integrated discovery to identify the pathways and functional annotation of DEGs. Protein-protein interaction of these DEGs was analyzed based on the search tool for the retrieval of interacting genes database and visualized by Cytoscape software. In addition, we used encyclopedia of RNA interactomes (ENCORI), gene expression profiling interactive analysis (GEPIA), and the human protein atlas to confirm the expression of hub genes in ESCC. Finally, GEPIA was used to evaluate the prognostic value of hub genes expression in ESCC patients and we estimated the associations between hub genes expression and immune cell populations (B Cell, CD8+ T Cell, CD4+ T Cell, Macrophage, Neutrophil, and Dendritic Cell) in esophageal carcinoma (ESCA) using tumor immune estimation resource (TIMER). RESULTS: In this study, 707 DEGs (including 385 upregulated genes and 322 downregulated genes) and 6 hub genes (cyclin B1 [CCNB1], cyclin dependent kinase 1 [CDK1], aurora kinase A [AURKA], ubiquitin conjugating enzyme E2C [UBE2C], cyclin A2 [CCNA2], and cell division cycle 20 [CDC20]) were identified. All of the 6 hub genes were highly expressed in ESCC tissues. Among of them, only CCNB1 and CDC20 were associated with stage of ESCC and all of them were not associated with survival time of patients. CONCLUSION: DEGs and hub genes were confirmed in our study, providing a thorough, scientific and comprehensive research goals for the pathogenesis of ESCC.
Assuntos
Biologia Computacional/métodos , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Humanos , Mapas de Interação de Proteínas/genéticaRESUMO
BACKGROUND: Esophageal cancer (EC) is a malignant tumor with high mortality. Correlations have been found between the expression level of tropomyosin 3 (TPM3) and the depth of tumor invasion, lymph node metastasis, and the 5-year survival rate. However, the specific mechanisms underlying EC remain unclear. METHODS: Stably transfected TPM3-overexpresing and TPM3-knockdown esophageal squamous cell carcinoma (ESCC) cell lines (ECa109 and EC9706) were constructed, and the association between TPM3 and the proliferation, invasion, and migration of ESCC was investigated using molecular biology methods. The associations between TPM3 and matrix metalloproteinase (MMP)2/9 or epithelial-mesenchymal transition (EMT)-related proteins were verified, and the potential tumor-promoting mechanism was explored by Gelatin Zymography Experiment. RESULTS: TPM3 was found to promote the proliferation, migration, and metastatic potential of ESCC in vivo and in vitro, and stimulate the expression of MMP2/9 and certain EMT markers other than E-cadherin. The replenishment of MMP2/9 restored the malignant behavior of ESCC caused by TPM3. A gelatinase assay showed that the expression of TPM3 was related to the activity of MMP9. CONCLUSIONS: TPM3 promoted proliferation, migration, and metastatic potential in EC cells. Additionally, TPM3 promoted the EMT process. This function may be achieved via the regulation the expression of MMP2/9.
RESUMO
Esophageal squamous cell carcinoma (ESCC) ranks as the fourth leading cause of cancer-related death in China. Although paclitaxel has been shown to be effective in treating ESCC, the prolonged use of this chemical will lead to paclitaxel resistance. In order to uncover genes and pathways driving paclitaxel resistance in the progression of ESCC, bioinformatics analyses were performed based on The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database including GSE86099 and GSE161533. Differential expression analysis was performed in TCGA data and two GEO datasets to obtain differentially expressed genes (DEGs). Based on GSE161533, weighted gene co-expression network analysis (WGCNA) was conducted to identify the key modules associated with ESCC tumor status. The DEGs common to the two GEO datasets and the genes in the key modules were intersected to obtain the paclitaxel resistance-specific or non-paclitaxel resistance-specific genes, which were subjected to subsequent least absolute shrinkage and selection operator (LASSO) feature selection, whereby paclitaxel resistance-specific or non-paclitaxel resistance-specific key genes were selected. Ten machine learning models were used to validate the biological significance of these key genes; the potential therapeutic drugs for paclitaxel resistance-specific genes were also predicted. As a result, we identified 24 paclitaxel resistance-specific genes and 18 non-paclitaxel resistance-specific genes. The ESCC machine classifiers based on the key genes achieved a relatively high AUC value in the cross-validation and in an independent test set, GSE164158. A total of 207 drugs (such as bevacizumab) were predicted to be alternative therapeutics for ESCC patients with paclitaxel resistance. These results might shed light on the in-depth research of paclitaxel resistance in the context of ESCC progression.