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PURPOSE: This study aimed to identify parameters with a higher diagnostic value for early screening of prostate cancer (PCa) at different ages. MATERIALS AND METHODS: A total of 294 patients were included and divided into two groups according to the age of patients (≤66 and >66 years). Receiver operating characteristic (ROC) curves of total prostate-specific antigen (TPSA), free PSA (FPSA), (F/T)PSA, PSA density (PSAD), PSA-AV score, the ratio of patients' age to prostate volume (AVR) and (F/T)/PSAD were constructed. The area under the ROC curve (AUC) was calculated, and differences in the AUC values among the above-mentioned parameters were compared. RESULTS: There were 121 patients in the ≤66 years age group (benign prostatic hyperplasia BPH, 103 patients; PCa 18 patients) and 173 patients in the >66 years age group (BPH, 100 patients; PCa, 73 patients). In the ≤66 years age group, the AUC value of AVR for PCa diagnosis was the highest; however, there was no statistically significant difference compared with the AUC values of PSAD and (F/T)/PSAD; compared with TPSA, FPSA, (F/T)PSA and PSA-AV, the differences were statistically significant. In the >66 years age group, the AUC values of PSAD and PSA-AV for PCa diagnosis were higher than those of TPSA, FPSA, (F/T)PSA and (F/T)/PSAD, and the difference was statistically significant; however, the difference was not statistically significant when compared with the AUC value of AVR. CONCLUSION: In different age groups, screening indices for PCa diagnosis should be selected according to the age of patients.
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Fatores Etários , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Idoso , Detecção Precoce de Câncer , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/epidemiologia , Curva ROCRESUMO
PURPOSE: The purpose of the study was to evaluate the diagnostic significance of two new and a few clinical markers for prostate cancer (PCa) at various prostate volumes (PV). METHODS: The study subjects were divided into two groups. Among them, there were 70 cases in the PV ≤30 ml group (benign prostatic hyperplasia [BPH]: 32 cases, PCa: 38 cases) and 372 cases in the PV > 30 ml group (BPH: 277 cases, PCa: 95 cases). SPSS 26.0 and GraphPad Prism 8.0 were used to construct their receiver operating characteristic (ROC) curves for diagnosing PCa and calculating their area under the ROC curve (AUC). RESULTS: In the PV ≤30 ml group, the diagnostic parameters based on prostate-specific antigen (PSA) had a decreased diagnostic significance for PCa. In the PV > 30 ml group, PSAD (AUC = 0.709), AVR (AVR = Age/PV, AUC = 0.742), and A-PSAD (A-PSAD = Age×PSA/PV, AUC = 0.736) exhibited moderate diagnostic significance for PCa, which was better than PSA-AV (AUC = 0.672), free PSA (FPSA, AUC = 0.509), total PSA (TPSA, AUC = 0.563), (F/T) PSA (AUC = 0.540), and (F/T)/PSAD (AUC = 0.663). Compared with AVR, A-PSAD exhibited similar diagnostic significance for PCa, but higher than PSA density (PSAD). CONCLUSIONS: Choosing appropriate indicators for different PVs could contribute to the early screening and diagnosis of PCa. The difference in the diagnostic value of two new indicators (A-PSAD and AVR), and PSAD for PCa may require further validation by increasing the sample size.
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Hiperplasia Prostática , Neoplasias da Próstata , Biomarcadores , Detecção Precoce de Câncer , Humanos , Masculino , Próstata/diagnóstico por imagem , Antígeno Prostático Específico , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Curva ROCRESUMO
Prostate cancer (PCa) is one of the most prevalent tumours of the male genitourinary system in the world. In recent years, the morbidity of PCa is steadily rising annually in China. Prostate cancer is prone to distant metastasis, and the most significant complication among patients with advanced PCa is bone metastases. Most patients with prostate cancer do not die of the primary tumour, but more due to the factors of distant metastasis of organs, especially bone metastasis. Due to the lack of effective prevention and monitoring of bone metastasis of PCa in clinical settings, and the lack of effective treatment for patients with bone metastasis, the prognosis of patients is often poor. Therefore, early prevention, early detection, and inhibition of bone metastasis are particularly important. At present, many studies have found that exosomes and integrins are closely related to bone metastasis of prostate cancer, but they have not been summarized together. This review summarizes the literature on the effects of exosomes and integrins on bone metastasis of prostate cancer in recent years. It aims to find more effective ways to prevent, monitor, and treat prostate cancer from the relationship between them.
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Neoplasias Ósseas , Exossomos , Neoplasias da Próstata , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Humanos , Integrinas , Masculino , Prognóstico , Neoplasias da Próstata/patologiaRESUMO
This study aimed to analyse the clinical characteristics and risk factors of patients with positive prostate biopsy at 4-20 ng/mL of prostate-specific antigen (PSA), construct a new parameter based on this characteristics and assess its diagnostic value for prostate cancer (PCa). Logistic regression analysis was used to clarify the risk factors of PCa, and a new parameter based on the results was constructed. Compare the diagnostic value of various diagnostic parameters for PCa. Logistic multivariate regression analysis revealed that age (OR, 5.269; 95%CI, 2.762-10.050), comorbid diabetes (OR, 2.437; 95%CI, 1.162-5.111), PSA (OR, 2.462; 95%CI, 1.198-5.059) and prostate volume (PV) (OR, 0.227; 95%CI, 0.100-0.516) are risk factors for PCa. The age, PSA and PV of patients were combined to construct a new parameter, that is A-PSAD = (age × total PSA [TPSA])/PV]. The area under the receiver-operating characteristic curve(AUC) of A-PSAD (0.728) for PCa diagnosis was higher than the AUCs of TPSA (0.581), free prostate-specific antigen (0.514), (F/T)PSA (0.535) and PSAD (0.696), with significant differences. Age, history of diabetes, TPSA and PV are risk factors for PCa(PSA:4-20ng/mL); in addition, A-PSAD has a moderate diagnostic value for PCa and may become a new indicator for PCa screening.
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Antígeno Prostático Específico , Neoplasias da Próstata , Biópsia , Detecção Precoce de Câncer , Humanos , Masculino , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Curva ROCRESUMO
BACKGROUND: Encouraged by the goal of developing an effective treatment strategy for prostate cancer, this study explored the mechanism involved in metformin-mediated inhibition of AR-negative prostate cancer. METHODS: Cell behaviors of DU145 and PC3 cells were determined by CCK8 test, colony formation experiment and scratch test. Flow cytometry was used to detect cell cycle distribution. Cell autophagy was induced with metformin, and an autophagy inhibitor, 3-MA, was used to assess the level of autophagy. Detection of LC3B by immunofluorescence was conducted to determine autophagy level. Cell proliferation, autophagy and cell cycle were examined by performing Western blot. DU145 and PC3 cell lines were transfected with AMPK siRNA targeting AMPK-α1 and AMPK-α2. Tumor formation experiment was carried out to evaluate the anti-prostate cancer effect of metformin in vivo. RESULTS: The inhibitory effect of metformin on the proliferation of prostate cancer cell lines was confirmed in this study, and the mechanism of such an effect was related to autophagy and the block of cell cycle at G0/G1 phase. Metformin also induced the activation of AMPK, markedly promoted expression of LC3II, and down-regulated the expression of p62/SQSTM1. Animal experiments showed that the tumor volume of metformin group was smaller, meanwhile, the levels of p-AMPK (Thr172) and LC3B were up-regulated and the Ki-67 level was down-regulated, without abnormalities in biochemical indicators. CONCLUSION: This study found that autophagy induction might be the mechanism through which metformin suppressed the growth of AR-negative prostate cancer. Moreover, the activation of AMPK/autophagy pathway might be a therapeutically effective for treating AR-negative prostate cancer in the future.
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A general and practical approach to benzimidazothiazepine and benzimidazothioether derivatives via an intramolecular nucleophilic addition/ring expansion rearrangement of aryl isothiocyanates promoted by the tert-amino effect has been developed. This reaction is catalyzed by low-cost camphorsulfonic acid and tolerates a broad substrate scope with complete atom economy. Structurally intriguing benzimidazothiazepine and benzimidazothioether products could be easily obtained by a simple operation in good to excellent yield (up to 98%).
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Background: Matrix Metalloproteinases (MMPs) play an indispensable role in the initial alteration and development of PCa. We tried to generate an MMP-related prognostic signature (MMPS) in prostate cancer (PCa). Methods: TCGA-PRAD, MSKCC/GSE21032, GSE116918, GSE70769 cohorts were enrolled to assess the prognostic value of MMPs. The least absolute shrinkage and selection operator (LASSO) Cox regression was employed to generate the MMPS signature. The log-rank test and Kaplan-Meier (K-M) survival curve were applied to show the difference RFS, The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) was plotted to predict the accuracy of signature. CIBERSORT was conducted to analyze the different immune infiltration in MMPS-H and MMPS-L groups. Potential signaling pathways activated in the MMPS-H groups by Metascape. Results: MMP1, MMP7, MMP11, MMP24 and MMP26 were selected by LASSO regression and established the MMPS predict signature. The MMPS showed the high prognostic value in TCGA-PRAD training cohort (AUC=0.714) and validation cohorts (GSE116918: AUC=0.976, GSE70769: AUC=0.738, MSKCC: AUC=0.793). Pid integrin1 pathway, G2M checkpoint, and response to growth factor signaling pathways were activated in MMPS-H group, patients with the high MMPS risk score and low M2 macrophage showed the worst recurrence-free survival (RFS). Conclusion: MMPs involved and played an essential role in the tumorigenesis and biochemical recurrence in PCa patients. The MMPS signature could accurately predict the recurrence of PCa patients and validated in several cohorts.
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Metaloproteinases da Matriz/metabolismo , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Intervalo Livre de Doença , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 11 da Matriz/genética , Metaloproteinase 11 da Matriz/metabolismo , Metaloproteinase 7 da Matriz/genética , Metaloproteinase 7 da Matriz/metabolismo , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz Associadas à Membrana/genética , Metaloproteinases da Matriz Associadas à Membrana/metabolismo , Metaloproteinases da Matriz Secretadas/genética , Metaloproteinases da Matriz Secretadas/metabolismo , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Neoplasias da Próstata/metabolismo , Curva ROCRESUMO
Cardiovascular diseases (CVDs) continue to pose a significant burden on global health, prominently contributing to morbidity and mortality rates worldwide. Recent years have witnessed an increasing recognition of the intricate involvement of neutrophil extracellular traps (NETs) in the pathology of diverse cardiovascular conditions. This review provides a comprehensive analysis of the multifaceted functions of NETs in cardiovascular diseases, shedding light on the impact on atherosclerosis, myocardial infarction, heart failure, myocarditis, atrial fibrillation, aortic stenosis, and the potential therapeutic avenues targeting NETs.
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Fulvic acid (FA) and humic acid (HA) are common polyacids in nature. However, the evolutionary process of their basic and advanced structures is still unclear. FA and HA were separated into five molecular weight components to investigate the process of evolution from small to large molecules. The primary structure analysis showed that FA were rich in CN, COOH and OH content, while HA were rich in (CH2)n, NH2 and CC. Moreover, with the molecular weight increasing, the structures could complement each other to maintain the hydrophilic or hydrophobic balance. The 2D-COS spectroscopy demonstrated that during the growth of FA, COOH, NH2 and OH firstly respond. On the other hand, during the growth of HA, NH2 and (CH2)n firstly respond. In addition, advanced structure of FA was affected by intramolecular hydrogen bonds and π - π interaction. HA was affected by hydrophobic interactions due to the abundance of hydrophobic groups, primarily (CH2)n and benzene rings. 3D conformational fitting and particle size characterization confirmed that the interaction forces determine that FA and HA become tightly and loosely molecules respectively. This study is to further explore the geochemical formation and evolution process of FA and HA molecules.
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Substâncias Húmicas , Eliminação de Resíduos , Substâncias Húmicas/análise , Perda e Desperdício de Alimentos , Alimentos , Benzopiranos/químicaRESUMO
Aerobic kitchen waste composting can contribute to greenhouse gas (GHGs) emissions and global warming. This study investigated the effects of biochar and zeolite on GHGs emissions during composting. The findings demonstrated that biochar could reduce N2O and CH4 cumulative releases by 47.7 %and 47.9 %, respectively, and zeolite could reduce the cumulative release of CO2 by 28.4 %. Meanwhile, the biochar and zeolite addition could reduce the abundance of potential core microorganisms associated with GHGs emissions. In addition, biochar and zeolite reduced N2O emissions by regulating the abundance of nitrogen conversion functional genes. Biochar and zeolite were shown to reduce the impact of bacterial communities on GHGs emissions. In summary, this study revealed that biochar and zeolite can effectively reduce GHG emissions during composting by altering the compost microenvironment and regulating microbial community structure. Such findings are valuable for facilitating high-quality resource recovery of organic solid waste.
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Compostagem , Gases de Efeito Estufa , Zeolitas , Gases de Efeito Estufa/análise , Zeolitas/química , Solo/química , Metano/análise , Carvão Vegetal , Nitrogênio/análise , Óxido Nitroso/análiseRESUMO
The pollution and harm of food waste (FW) are increasingly concerned, which has the dual attributes of pollutants and resources. This study aimed to improve the synthesis efficiency of FW humic substances (HS), and investigating the effect of catechol on the formation mechanism and structure of humic acid (HA) and fulvic acid (FA). Results indicated that catechol incorporation could enable to exhibit higher HS yield and more complex structure, especially the maximum particle size of FA reached 4800 nm. This was due to the combination of catechol with multiple nitrogenous compounds, which accelerated molecular condensation. Spectroscopic scans analysis revealed that Maillard reaction occurs first. Subsequently, Maillard reaction products and amino acids were combined with different sites of catechol, which leads to the difference of molecular structure of HS. The structure of FA is characterized by an abundance of carboxyl and hydroxyl groups, whereas HA is rich in benzene and heterocyclic structures. The structural difference was responsible for the disparity in the functional properties of FA and HA. Specifically, the presence of amino, hydroxyl, pyridine, and carboxyl groups in FA contributes significantly to its chelating activity. This research provides an efficient and sustainable unique solution for the high-value of FW conversion, and provides evidence for understanding the structural evolution of HA and FA.
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Eliminação de Resíduos , Solo , Solo/química , Perda e Desperdício de Alimentos , Reação de Maillard , Alimentos , Polimerização , Eliminação de Resíduos/métodos , Substâncias Húmicas/análise , Catecóis , Benzopiranos/químicaRESUMO
Background: Ulcerative colitis (UC) is an intestinal inflammatory disease that is strongly associated with mitochondrial damage and dysfunction as well as mitophagy and lacks of satisfactory treatments. Hair follicle mesenchymal stem cell (HF-MSC)-derived exosomes owe benefit effectiveness on inflammatory therapies. Hypoxia-preconditioned HF-MSCs exhibit enhanced proliferation and migration abilities, and their exosomes exert stronger effects than normal exosomes. However, the therapeutic function of Hy-Exos in UC is unknown. Methods: The inflammation model was established with LPS-treated MODE-K cells, and the mouse UC model was established by dextran sulfate sodium (DSS) administration. The therapeutic effects of HF-MSC-derived exosomes (Exos) and hypoxia-preconditioned HF-MSC-derived exosomes (Hy-Exos) were compared in vitro and in vivo. Immunofluorescence staining and western blotting were used to explore the effects of Hy-Exos on mitochondrial function, mitochondrial fission and fusion and mitophagy. MiRNA sequencing analysis was applied to investigate the differences in components between Exos and Hy-Exos. Results: Hy-Exos had a better therapeutic effect on LPS-treated MODE-K cells and DSS-induced UC mice. Hy-Exos promoted colonic tight junction proteins expression, suppressed the oxidative stress response, and reduced UC-related inflammatory injury. Hy-Exos may exert these effects via miR-214-3p-mediated inhibition of the PI3K/AKT/mTOR signaling pathway, maintenance of mitochondrial dynamic stability, alleviation of mitochondrial dysfunction and enhancement of mitophagy. Conclusion: This study revealed a vital role for Hy-Exos in suppressing inflammatory progression in UC and suggested that miR-214-3p is a potential critical target for Hy-Exos in alleviating UC.
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Colite Ulcerativa , Modelos Animais de Doenças , Exossomos , Folículo Piloso , Células-Tronco Mesenquimais , Mitofagia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Colite Ulcerativa/metabolismo , Colite Ulcerativa/terapia , Colite Ulcerativa/patologia , Células-Tronco Mesenquimais/metabolismo , Exossomos/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Folículo Piloso/metabolismo , Sulfato de Dextrana , Masculino , Mitocôndrias/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , MicroRNAs/genética , HumanosRESUMO
The sulfate reduction reaction releases malodorous gases (H2S) during composting, with potential pollution risks to the environment. In this study, chicken manure (CM) with high sulfur content and beef cattle manure (BM) with low sulfur content were used to investigate the effect of control (CK) and low moisture content (LW) on sulfur metabolism. The results showed that compared to CK composting, the cumulative H2S emission of CM and BM composting decreased by 27.27% and 21.08% under LW condition, respectively. Meanwhile, the abundance of core microorganisms related to sulfur components was reduced under LW condition. Furthermore, the KEGG sulfur pathway and network analysis suggested that LW composting weakened the sulfate reduction pathway, and reduced the number and abundance of functional microorganisms and genes. These results indicated that low moisture content had important effects on inhibiting the release of H2S during composting, which provided a scientific basis to control environmental pollution.
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Compostagem , Sulfeto de Hidrogênio , Animais , Bovinos , Esterco , Gases , Enxofre , Galinhas , Sulfatos , Solo , Nitrogênio/análiseRESUMO
Researchers have shown that bone mesenchymal stem cells (BMSCs) can alleviate the progression of liver cirrhosis; however, it is unclear how exactly BMSCs function to cure liver disease. In this study, we used bioinformatics methods to assess differentially expressed genes (DEGs) in liver cirrhosis and found a significantly upregulated gene, Fstl1, in liver cirrhosis. In vivo and in vitro experiments showed that compared with those in the disease model group, the mRNA, and protein expression levels of Fstl1 were significantly reduced after BMSCs treatment, and the ß-Catenin protein level was also significantly reduced after BMSCs treatment. Subsequently, we downregulated Fstl1 in activated hepatic stellate cells (HSCs) and found that Wnt and ß-Catenin protein expression levels also decreased. Finally, we found that in BMSCs-treated activated HSCs, overexpression of Fstl1 reversed the inhibitory effect of BMSCs on the Wnt/ß-Catenin signaling pathway to a certain extent. In summary, our results show that BMSCs can inhibit Wnt/ß-Catenin signaling pathway activation by downregulating the protein expression level of Fstl1, thus alleviating cirrhosis. Therefore, targeted regulation of Fstl1 may provide a new therapeutic strategy for the progression of liver cirrhosis.
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Bone marrow mesenchymal stromal cells (BMSCs) have a protective effect against liver cirrhosis. Long noncoding RNAs (lncRNAs) play crucial roles in the progression of liver cirrhosis. Therefore, it is aimed to clarify the lncRNA Kcnq1ot1 involved protective mechanism of BMSCs in liver cirrhosis. This study found that BMSCs treatment attenuates CCl4 -induced liver cirrhosis in mice. Additionally, the expression of lncRNA Kcnq1ot1 is upregulated in human and mouse liver cirrhosis tissues, in addition to TGF-ß1-treated LX2 cells and JS1 cells. The expression of Kcnq1ot1 in liver cirrhosis is reversed with BMSCs treatment. The knockdown of Kcnq1ot1 alleviated liver cirrhosis both in vivo and in vitro. Fluorescence in situ hybridization (FISH) confirms that Kcnq1ot1 is mainly distributed in the cytoplasm of JS1 cells. It is predicted that miR-374-3p can directly bind with lncRNA Kcnq1ot1 and Fstl1, which is verified via luciferase activity assay. The inhibition of miR-374-3p or the overexpression of Fstl1 can attenuate the effect of Kcnq1ot1 knockdown. In addition, the transcription factor Creb3l1 is upregulated during JS1 cells activation. Moreover, Creb3l1 can directly bind to the Kcnq1ot1 promoter and positively regulate its transcription. In conclusion, BMSCs alleviate liver cirrhosis by modulating the Creb3l1/lncRNA Kcnq1ot1/miR-374-3p/Fstl1 signaling pathway.
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Proteínas Relacionadas à Folistatina , Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Humanos , Animais , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Relacionadas à Folistatina/genética , Medula Óssea/metabolismo , Hibridização in Situ Fluorescente , Células-Tronco Mesenquimais/metabolismo , Cirrose Hepática/genéticaRESUMO
This study built and tested two effective nomograms for the purpose of predicting cancer-specific survival and overall survival of chromophobe renal cell carcinoma (chRCC) patients. Multivariate Cox regression analysis was employed to filter independent prognostic factors predictive of cancer-specific survival and overall survival, and the nomograms were built based on a training set incorporating 2901 chRCC patients in a retrospective study (from 2004 to 2015) downloaded from the surveillance, epidemiology, and end results (SEER) database. The nomograms were verified on a validation cohort of 1934 patients, subsequently the performances of the nomograms were examined according to the receiver operating characteristic curve, calibration curves, the concordance (C-index), and decision curve analysis. The results showed that tumor grade, AJCC and N stages, race, marital status, age, histories of chemotherapy, radiotherapy and surgery were the individual prognostic factors for overall survival, and that AJCC, N and SEER stages, histories of surgery, radiotherapy and chemotherapy, age, tumor grade were individual prognostic factors for cancer-specific survival. According to C-indexes, receiver operating characteristic curves, and decision curve analysis outcomes, the nomograms showed a higher accuracy in predicting overall survival and OSS when compared with TNM stage and SEER stage. All the calibration curves were significantly consistent between predictive and validation sets. In this study, the nomograms, which were validated to be highly accurate and applicable, were built to facilitate individualized predictions of the cancer-specific survival and overall survival to patients diagnosed with chRCC between 2004 and 2015.
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Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Nomogramas , Idoso , Área Sob a Curva , Calibragem , Tomada de Decisão Clínica , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROCRESUMO
BACKGROUND: Prostate cancer (PC) is one of the most common malignancies in males. Extensive and complex connections between circadian rhythm and cancer were found. Nonetheless, in PC, the potential role of the core components of the mammalian circadian clock (CCMCCs) in prognosis prediction has not been fully clarified. METHODS: We firstly collected 605 patients with PC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Survival analysis was carried out for each CCMCC. Then, we investigated the prognostic ability of CCMCCs by Cox regression analysis. Independent prognostic signatures were extracted for the establishment of the circadian clock-based risk score model. We explored the predictive performance of the risk score model in the TCGA training cohort and the independent GEO dataset. Finally, the relationships between risk score and clinicopathological parameters, biological processes, and signaling pathways were evaluated. RESULTS: The expression levels of CCMCCs were widely correlated with age, tumor status, lymph node status, disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). Nine circadian clock genes, including CSNK1D, BTRC, CLOCK, CSNK1E, FBXL3, PRKAA2, DBP, NR1D2, and RORB, were identified as vital prognostic factors in PC and were used to construct the circadian clock-based risk score model. For DFS, the area under the 3-year or 5-year receiver operating characteristic curves ranged from 0.728 to 0.821, suggesting better predictive performance. When compared with T3-4N1 stage, PC patients at T2N0 stage might be benefited more from the circadian clock-based risk score model. Furthermore, a high circadian clock-based risk score indicated shorter DFS (p < 0.0001), early progression (p < 0.0001), and higher 5-year death rate (p = 0.007) in PC. The risk score was related to tumor status (p < 0.001), lymph node status (p < 0.001), and ribosome-related biogenesis and pathways. CONCLUSIONS: The vital roles of circadian clock genes in clinical outcomes were fully depicted. The circadian clock-based risk score model could reflect and predict the prognosis of patients with PC.
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Tumor necrosis factor alpha-induced protein 3 (TNFAIP3), a deubiquitinating enzyme, plays an essential regulatory role in inflammation, immune responses and tumorigenesis. Our present study indicates that TNFAIP3 is required for the ubiquitination degradation of epithelial-mesenchymal transition (EMT) related transcription factors Snail and ZEB1, which further altered the expression of EMT-related marker proteins and eventually contributing to the malignant phenotype and poorer prognosis of gastric carcinoma. Depletion of TNFAIP3 attenuated the capacity of proliferation, migration and invasion of gastric cancer cells in vitro. Taken together, these findings propose a pathway linking the TNFAIP3 to the EMT-mediated metastatic process in gastric cancer, which provides a viable strategy regarding the interventions and prognostic analysis of gastric carcinoma in clinical practice.
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Transformação Celular Neoplásica/genética , Invasividade Neoplásica/genética , Neoplasias Gástricas/patologia , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Neoplasias Gástricas/genética , Fatores de Transcrição/metabolismoRESUMO
This study aimed to analyze prognostic significance of aldehyde dehydragenase 1 (ALDH1) and Nodal expression in patients with colorectal cancer. ALDH1 and Nodal expressions were observed based on the immunohistochemistry staining from 108 colorectal cancer patients. Scores were given to the staining intensity and percentage of positive cells, and sum of two scores for each case was used to define the groups of ALDH1 and Nodal. We also investigated the protein and mRNA levels of ALDH1 and Nodal by Western blot and qRT-PCR assays. The results were analyzed with the clinicopathologic parameters of these patients. The results indicated that expressions of ALDH1 and Nodal were significantly correlated with the differentiation degree, metastasis, number of tumor positive lymph nodes and AJCC stage. ALDH1 was inclined to express more in the worse differentiated degrees, lymph node metastasis, and worse AJCC stage of colorectal cancer patients. And the expression of Nodal was inversely compared with ALDH1.While the expression of ALDH1 was inversely correlated with the Nodal (r = -0.709, P < 0.01).