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  • Frontiers Media SA  (14)
  • 1
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-12-21)
    Abstract: The aim of this study was to establish and validate a nomogram model for accurate prediction of patients’ survival with T1aN0M0 none small cell lung cancer (NSCLC). Methods The patients, diagnosed with the stage IA NSCLC from 2004–2015, were identified from the Surveillance, Epidemiology and End Results (SEER) database. The variables with a P -value & lt; 0.05 in a multivariate Cox regression were selected to establish the nomogram. The discriminative ability of the model was evaluated by the concordance index (C-index). The proximity of the nomogram prediction to the actual risk was depicted by a calibration plot. The clinical usefulness was estimated by the decision curve analysis (DCA). Survival curves were made with Kaplan–Meier method and compared by Log–Rank test. Results Eight variables, including treatment, age, sex, race, marriage, tumor size, histology, and grade were selected to develop the nomogram model by univariate and multivariate cox regression. The C-index was 0.704 (95% CI, 0.694–0.714) in the training set and 0.713 (95% CI, 0.697–0.728) in the test set, which performed significantly better than 8th edition AJCC TNM stage system (0.550, 95% CI, 0.408–0.683, P & lt; 0.001). The calibration curve showed that the prediction ability of 3-years and 5-years survival rate demonstrated a high degree of agreement between the nomogram model and the actual observation. The DCA curves also proved that the nomogram-assisted decisions could improve patient outcomes. Conclusion We established and validated a prognostic nomogram to predict 3-years and 5-years overall survival in stage IA NSCLC.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 2
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-3-27)
    Abstract: Hepatocellular carcinoma (HCC) is one of the most invasive cancers with a low 5-year survival rate. Pyroptosis, a specialized form of cell death, has shown its association with cancer progression. However, its role in the prognosis of HCC has not been fully understood. Methods In our study, clinical information and mRNA expression for 1076 patients with HCC were obtained from the five public cohorts. Pyroptotic clusters were generated by unsupervised clustering based on 40 pyroptosis-related genes (PRGs) in the TCGA and ICGC cohort. A pyroptosis-related signature was constructed using least absolute shrinkage and selection operator (LASSO) regression according to differentially expressed genes (DEGs) of pyroptotic clusters. The signature was then tested in the validation cohorts (GES10142 and GSE14520) and subsequently validated in the CPTAC cohort (n=159) at both mRNA and protein levels. Response to sorafenib was explored in GSE109211. Results Three clusters were identified based on the 40 PRGs in the TCGA cohort. A total of 24 genes were selected based on DEGs of the above three pyroptotic clusters to construct the pyroptotic risk score. Patients with the high-risk score showed shorter overall survival (OS) compared to those with the low-risk score in the training set (P & lt;0.001; HR, 3.06; 95% CI, 2.22-4.24) and the test set (P=0.008; HR, 1.61; 95% CI, 1.13-2.28). The predictive ability of the risk score was further confirmed in the CPTAC cohort at both mRNAs (P & lt;0.001; HR, 2.99; 95% CI, 1.67-5.36) and protein levels (P & lt;0.001; HR, 2.97; 95% CI 1.66-5.31). The expression of the model genes was correlated with immune cell infiltration, angiogenesis-related genes, and sensitivity to antiangiogenic therapy (P & lt;0.05). Discussion In conclusion, we established a prognostic signature of 24 genes based on pyroptosis clusters for HCC patients, providing insight into the risk stratification of HCC.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 3
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    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Physiology Vol. 11 ( 2020-7-17)
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 11 ( 2020-7-17)
    Type of Medium: Online Resource
    ISSN: 1664-042X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2564217-0
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  • 4
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    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-11-23)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-11-23)
    Abstract: The optimal interventional strategy remains undetermined in hemodynamically stable patients with NSTEMI and MVD. This study aimed to examine clinical prognosis among culprit vessel, immediate multivessel, and staged percutaneous coronary intervention (PCI) in patients with NSTEMI and MVD. Methods This retrospective, observational, single-center study included 943 hemodynamically stable patients with NSTEMI and MVD who had undergone successful drug-eluting stent (DES) implantation from January 2014 to December 2019. Patients were categorized into culprit lesion-only PCI (CL-PCI), immediate multivessel PCI (MV-PCI), and out-of-hospital staged MV-PCI according to PCI strategy. The primary outcome was the composite of major adverse cardiac events (MACEs), including all-cause death, myocardial infarction (MI), or unplanned repeat revascularization. The secondary outcomes were all-cause death, cardiac death, MI, and unplanned repeat revascularization. Results Over a median follow-up of 59 months, immediate MV-PCI was associated with a lower risk of all-cause death than CL-PCI (HR: 0.591, 95%CI: 0.364–0.960, P = 0.034). Out-of-hospital staged MV-PCI was associated with a reduced risk of MACE (HR: 0.448, 95%CI: 0.314–0.638, P & lt; 0.001) and all-cause death (HR: 0.326, 95%CI: 0.183–0.584, P & lt; 0.001) compared with CL-PCI. The above results were accordant after multivariate COX analysis and propensity score matching. MACE (HR: 0.560, 95%CI: 0.385–0.813, P = 0.002) and repeat revascularization (HR: 0.627, 95%CI: 0.400–0.982, P = 0.041) were significantly less likely to occur with out-of-hospital MV-PCI rather than immediate MV-PCI. However, the incidences of primary and secondary outcomes were comparable between immediate and staged PCI after confounder adjustment using multivariate regression and propensity score matching analysis. For subgroup analyses stratified by synergy between PCI with taxus and cardiac surgery score, staged MV-PCI was found to lower the risk of MACE compared with immediate MV-PCI in patients with more complex coronary disease. Conclusion Hemodynamically stable patients with NSTEMI and MVD benefited from the strategy of MV-PCI. Patients with complex coronary anatomy treated with out-of-hospital staged MV-PCI rather than immediate MV-PCI had lower risks of MACE. These need to be confirmed in the future randomized study.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 5
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    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Genetics Vol. 12 ( 2021-11-17)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 12 ( 2021-11-17)
    Abstract: 5-Hydroxymethylcytosine (5hmC), the oxidative product of 5-methylcytosine (5mC) catalyzed by ten-eleven translocation enzymes, plays an important role in many biological processes as an epigenetic mediator. Prior studies have shown that 5hmC can be selectively labeled with chemically modified glucose moieties and enriched using click chemistry with biotin affinity approaches. Besides, DNA deaminases of the AID/APOBEC family can discriminate modified 5hmC bases from cytosine (C) or 5mC. Herein, we developed a method based on embryonic stem cell (ESC) whole-genome analysis, which could enrich 5hmC-containing DNA by selective chemical labeling and locate 5hmC sites at single-base resolution with enzyme-based deamination. The combination experimental design is an extension of previous methods, and we hope that this cost-effective single-base resolution 5hmC sequencing method could be used to promote the mechanism and diagnosis research of 5hmC.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606823-0
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  • 6
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    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Molecular Biosciences Vol. 9 ( 2022-6-22)
    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 9 ( 2022-6-22)
    Abstract: DNA damage response (DDR) pathways play a crucial role in lung cancer. In this retrospective analysis, we aimed to develop a prognostic model and molecular subtype based on the expression profiles of DDR-related genes in early-stage lung adenocarcinoma (LUAD). A total of 1,785 lung adenocarcinoma samples from one RNA-seq dataset of The Cancer Genome Atlas (TCGA) and six microarray datasets of Gene Expression Omnibus (GEO) were included in the analysis. In the TCGA dataset, a DNA damage response gene (DRG)–based signature consisting of 16 genes was constructed to predict the clinical outcomes of LUAD patients. Patients in the low-DRG score group had better outcomes and lower genomic instability. Then, the same 16 genes were used to develop DRG-based molecular subtypes in the TCGA dataset to stratify early-stage LUAD into two subtypes (DRG1 and DRG2) which had significant differences in clinical outcomes. The Kappa test showed good consistency between molecular subtype and DRG (K = 0.61, p & lt; 0.001). The DRG subtypes were significantly associated with prognosis in the six GEO datasets (pooled estimates of hazard ratio, OS: 0.48 (0.41–0.57), p & lt; 0.01; DFS: 0.50 (0.41–0.62), p & lt; 0.01). Furthermore, patients in the DRG2 group benefited more from adjuvant therapy than standard-of-care, which was not observed in the DRG1 group. In summary, we constructed a DRG-based molecular subtype that had the potential to predict the prognosis of early-stage LUAD and guide the selection of adjuvant therapy for early-stage LUAD patients.
    Type of Medium: Online Resource
    ISSN: 2296-889X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2814330-9
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Cell and Developmental Biology Vol. 11 ( 2023-1-12)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 11 ( 2023-1-12)
    Abstract: Background: Glioblastoma multiforme (GBM) is the most common and invasive primary central nervous system tumor. The prognosis after surgery, radiation and chemotherapy is very poor. Bromodomain (BRD) proteins have been identified in oncogenic rearrangements, and play a key role in the development of multiple cancers. However, the relationship between BET proteins and prognosis of GBM are still worth exploring, and the distinct functions of BET proteins and tumor immunology in GBM have not been fully elucidated. Therefore, it is particularly important to develop effective biomarkers to predict the prognosis of GBM patients. Methods: Metascape, David, Kaplan-Meier Plotter, Oncomine, GEPIA, TCGA, TIMER, and LinkedOmics databases were used to assess the expression and prognosis for BET proteins in GBM. ROC analysis of risk model was established to identify the correlation between BET genes and overall survival in GBM patients. TIMER and GEPIA databases were used to comprehensively investigate the correlation between BET genes and tumor immune infiltration cells. Moreover, the image of immunohistochemistry staining of BET proteins in normal tissue and tumor tissue were retrived from the HPA database. In addition, differential analysis and pathway enrichment analysis of BRD4 gene expression profile were also carried out. Finally, immune-fluorescence and Western blot were used to clarify the expression of BRD4 in GBM cells. Results: Bioinformatics analysis showed that the expression levels of BET genes in GBM may play an important role in oncogenesis. Specifically, bioinformatic and immunohistochemistry analysis showed that BRD4 protein was more highly expressed in tumor tissues than that in normal tissues. The high expression of BRD4 was associated with poor prognosis in GBM. The expression of BET genes were closely related to the immune checkpoint in GBM. The correlation effect of BRD4 was significantly higher than other BET genes, which represented negative correlation with immune checkpoint. The expression of BRD4 was positively associated with tumor purity, and negatively associated with immune infiltration abundance of macrophage, neutrophil and CD8 + T-cell, respectively. Cox analysis showed that the model had good survival prediction and prognosis discrimination ability. In addition, the expression levels of BRD4 protein was significantly higher in U-251 MG cells than that in normal cells, which was consistent with the results of bioinformatics data. Conclusion: This study implied that BRD4 could be hopeful prognostic biomarker in GBM. The increased expression of BRD4 may act as a molecular marker to identify GBM patients with high-risk subgroups. BRD4 may be a valuable prognostic biomarker, and a potential target of precision therapy against GBM.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2737824-X
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  • 8
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    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-7-22)
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-7-22)
    Abstract: Hepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogs, cannot achieve life-long cure, and clarification of antiviral host immunity is necessary for eradication. Here, we found that a clathrin-binding membrane protein epsin3 (EPN3) negatively regulates the expression of HBV RNA. EPN3 expression was induced by transfection of an HBV replicon plasmid, and reduced HBV-RNA level in hepatic cell lines and murine livers hydrodynamically injected with the HBV replicon plasmid. Viral RNA reduction by EPN3 was dependent on transcription, and independent from epsilon structure of viral RNA. Viral RNA reduction by overexpression of p53 or IFN-α treatment, was attenuated by knockdown of EPN3, suggesting its role downstream of IFN-α and p53. Taken together, this study demonstrates the anti-HBV role of EPN3. The mechanism how it decreases HBV transcription is discussed.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 9
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    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 13 ( 2023-1-12)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2023-1-12)
    Abstract: Influenza susceptibility difference is a widely existing trait that has great practical significance for the accurate prevention and control of influenza. Methods Here, we focused on the human susceptibility to the seasonal influenza A/H3N2 of healthy adults at baseline level. Whole blood expression data for influenza A/H3N2 susceptibility from GEO were collected firstly (30 symptomatic and 19 asymptomatic). Then to explore the differences at baseline, a suite of systems biology approaches - the differential expression analysis, co-expression network analysis, and immune cell frequencies analysis were utilized. Results We found the baseline condition, especially immune condition between symptomatic and asymptomatic, was different. Co-expression module that is positively related to asymptomatic is also related to immune cell type of naïve B cell. Function enrichment analysis showed significantly correlation with “B cell receptor signaling pathway”, “immune response−activating cell surface receptor signaling pathway” and so on. Also, modules that are positively related to symptomatic are also correlated to immune cell type of neutrophils, with function enrichment analysis showing significantly correlations with “response to bacterium”, “inflammatory response”, “cAMP−dependent protein kinase complex” and so on. Responses of symptomatic and asymptomatic hosts after virus exposure show differences on resisting the virus, with more effective frontline defense for asymptomatic hosts. A prediction model was also built based on only baseline transcription information to differentiate symptomatic and asymptomatic population with accuracy of 0.79. Discussion The results not only improve our understanding of the immune system and influenza susceptibility, but also provide a new direction for precise and targeted prevention and therapy of influenza.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 10
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    Online Resource
    Frontiers Media SA ; 2018
    In:  Frontiers in Immunology Vol. 9 ( 2018-7-31)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 9 ( 2018-7-31)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2606827-8
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