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  • Liu, Zaoqu  (12)
  • Unknown  (12)
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  • Unknown  (12)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Genetics Vol. 13 ( 2022-3-25)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-3-25)
    Abstract: Background: Due to high invasiveness and heterogeneity, the morbidity and mortality of intrahepatic cholangiocarcinoma (ICC) remain unsatisfied. Recently, the exploration of genomic variants has decoded the underlying mechanisms of initiation and progression for multiple tumors, while has not been fully investigated in ICC. Methods: We comprehensively analyzed 899 clinical and somatic mutation data of ICC patients from three large-scale cohorts. Based on the mutation landscape, we identified the common high-frequency mutation genes (FMGs). Subsequently, the clinical features, prognosis, tumor mutation burden (TMB), and pharmacological landscape from patients with different mutation carriers were further analyzed. Results: We found TP53 and KRAS were the common FMGs in the three cohorts. Kaplan–Meier survival curves and univariate and multivariate analysis displayed that TP53 and KRAS mutations were associated with poor prognosis. Considering the co-mutation phenomenon of TP53 and KRAS, we stratified patients into “Double-WT,” “Single-Hit,” and “Double-Hit” phenotypes by mutation status. Patients with the three phenotypes showed significant differences in the mutation landscape. Additionally, compared with “Double-WT” and “Single-Hit” phenotypes, patients with “Double-Hit” presented a dismal prognosis and significantly high TMB. Through chemotherapy sensitivity analysis, we identified a total of 30 sensitive drugs for ICC patients, of which 22 were drugs sensitive to “Double-WT,” 7 were drugs sensitive to “Double-Hit,” and only one was a drug sensitive to “Single-Hit.” Conclusion: Our study defined a novel mutation classification based on the common FMGs, which may contribute to the individualized treatment and management of ICC patients.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-2-9)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-2-9)
    Abstract: Formation and rupture of abdominal aortic aneurysm (AAA) is fatal, and the pathological processes and molecular mechanisms underlying its formation and development are unclear. Perivascular adipose tissue (PVAT) has attracted extensive attention as a newly defined secretory organ, and we aim to explore the potential association between PVAT and AAA. Methods We analyzed gene expression and clinical data of 30 PVAT around AAA and 30 PVAT around normal abdominal aorta (NAA). The diagnostic markers and immune cell infiltration of PVAT were further investigated by WGCNA, CIBERSORT, PPI, and multiple machine learning algorisms (including LASSO, RF, and SVM). Subsequently, eight-week-old C57BL/6 male mice ( n = 10) were used to construct AAA models, and aorta samples were collected for molecular validation. Meanwhile, fifty-five peripheral venous blood samples from patients (AAA vs. normal: 40:15) in our hospital were used as an inhouse cohort to validate the diagnostic markers by qRT-PCR. The diagnostic efficacy of biomarkers was assessed by receiver operating characteristic (ROC) curve, area under the ROC (AUC), and concordance index (C-index). Results A total of 75 genes in the Grey60 module were identified by WGCNA. To select the genes most associated with PVAT in the grey60 module, three algorithms (including LASSO, RF, and SVM) and PPI were applied. EGR1 and KLF4 were identified as diagnostic markers of PVAT, with high accurate AUCs of 0.916, 0.926, and 0.948 (combined two markers). Additionally, the two biomarkers also displayed accurate diagnostic efficacy in the mice and inhouse cohorts, with AUCs and C-indexes all & gt;0.8. Compared with the NAA group, PVAT around AAA was more abundant in multiple immune cell infiltration. Ultimately, the immune-related analysis revealed that EGR1 and KLF4 were associated with mast cells, T cells, and plasma cells. Conclusion EGR1 and KLF4 were diagnostic markers of PVAT around AAA and associated with multiple immune cells.
    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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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-3-17)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-3-17)
    Abstract: Background: Ischemic events after carotid endarterectomy (CEA) in carotid artery stenosis patients are unforeseeable and alarming. Therefore, we aimed to establish a novel model to prevent recurrent ischemic events after CEA. Methods: Ninety-eight peripheral blood mononuclear cell samples were collected from carotid artery stenosis patients. Based on weighted gene co-expression network analysis, we performed whole transcriptome correlation analysis and extracted the key module related to ischemic events. The biological functions of the 292 genes in the key module were annotated via GO and KEGG enrichment analysis, and the protein-protein interaction (PPI) network was constructed via the STRING database and Cytoscape software. The enrolled samples were divided into train ( n = 66), validation ( n = 28), and total sets ( n = 94). In the train set, the random forest algorithm was used to identify critical genes for predicting ischemic events after CEA, and further dimension reduction was performed by LASSO logistic regression. A diagnosis model was established in the train set and verified in the validation and total sets. Furthermore, fifty peripheral venous blood samples from patients with carotid stenosis in our hospital were used as an independent cohort to validation the model by RT-qPCR. Meanwhile, GSEA, ssGSEA, CIBERSORT, and MCP-counter were used to enrichment analysis in high- and low-risk groups, which were divided by the median risk score. Results: We established an eight-gene model consisting of PLSCR1 , ECRP , CASP5 , SPTSSA , MSRB1 , BCL6 , FBP1 , and LST1 . The ROC-AUCs and PR-AUCs of the train, validation, total, and independent cohort were 0.891 and 0.725, 0.826 and 0.364, 0.869 and 0.654, 0.792 and 0.372, respectively. GSEA, ssGSEA, CIBERSORT, and MCP-counter analyses further revealed that high-risk patients presented enhanced immune signatures, which indicated that immunotherapy may improve clinical outcomes in these patients. Conclusion: An eight-gene model with high accuracy for predicting ischemic events after CEA was constructed. This model might be a promising tool to facilitate the clinical management and postoperative surveillance of carotid artery stenosis patients.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 9 ( 2022-1-10)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2022-1-10)
    Abstract: The immune microenvironment has profound impacts on the initiation and progression of colorectal cancer (CRC). Therefore, the goal of this article is to identify two robust immune subtypes in CRC, further provide novel insights for the underlying mechanisms and clinical management. In this study, two CRC immune subtypes were identified using the consensus clustering of immune-related gene expression profiles in the meta -GEO dataset (n = 1,198), and their reproducibility was further verified in the TCGA-CRC dataset (n = 638). Subsequently, we characterized the immune escape mechanisms, gene alterations, and clinical features of two immune subtypes. Cluster 1 (C1) was defined as the “immune cold subtype” with immune cell depletion and deficiency, while cluster 2 (C2) was designed as the “immune hot subtype”, with abundant immune cell infiltration and matrix activation. We also underlined the potential immune escape mechanisms: lack of MHC molecules and defective tumor antigen presentation capacity in C1, increased immunosuppressive molecules in C2. The prognosis and sensitivity to 5-FU, Cisplatin and immunotherapy differed between two subtypes. According to the two immune subtypes, we developed a prognosis associated risk score (PARS) with the accurate performance for predicting the prognosis. Additionally, two nomograms for overall survival (OS) and disease-free survival (DFS) were further constructed to facilitate clinical management. Overall, our research provides new references and insights for understanding and refining the CRC.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Genetics Vol. 12 ( 2021-5-17)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 12 ( 2021-5-17)
    Abstract: Background : Esophageal adenocarcinoma (EAC) remains a leading cause of cancer-related deaths worldwide and demonstrates a predominant rising incidence in Western countries. Recently, immunotherapy has dramatically changed the landscape of treatment for many advanced cancers, with the benefit in EAC thus far been limited to a small fraction of patients. Methods : Using somatic mutation data of The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium, we delineated the somatic mutation landscape of EAC patients from US and England. Based on the expression data of TCGA cohort, multiple bioinformatics algorithms were utilized to perform function annotation, immune cell infiltration analysis, and immunotherapy response assessment. Results : We found that RYR2 was a common frequently mutated gene in both cohorts, and patients with RYR2 mutation suggested higher tumor mutation burden (TMB), better prognosis, and superior expression of immune checkpoints. Moreover, RYR2 mutation upregulated the signaling pathways implicated in immune response and enhanced antitumor immunity in EAC. Multiple bioinformatics algorithms for assessing immunotherapy response demonstrated that patients with RYR2 mutation might benefit more from immunotherapy. In order to provide additional reference for antitumor therapy of different RYR2 status, we identified nine latent antitumor drugs associated with RYR2 status in EAC. Conclusion : This study reveals a novel gene whose mutation could be served as a potential biomarker for prognosis, TMB, and immunotherapy of EAC patients.
    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
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-2-10)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-2-10)
    Abstract: Introduction: Pyroptosis was recently implicated in the initiation and progression of tumors, including glioblastoma (GBM). This study aimed to explore the clinical significance of pyroptosis-related lncRNAs (PRLs) in GBM. Methods: Three independent cohorts were retrieved from the TCGA and CGGA databases. The consensus clustering and weighted gene coexpression network analysis (WGCNA) were applied to identify PRLs. The LASSO algorithm was employed to develop and validate a pyroptosis-related lncRNA signature (PRLS) in three independent cohorts. The molecular characteristics, clinical significances, tumor microenvironment, immune checkpoints profiles, and benefits of chemotherapy and immunotherapy regarding to PRLS were also explored. Results: In the WGCNA framework, a key module that highly correlated with pyroptosis was extracted for identifying PRLs. Univariate Cox analysis further revealed the associations between PRLs and overall survival. Based on the expression profiles of PRLs, the PRLS was initially developed in TCGA cohort ( n  = 143) and then validated in two CGGA cohorts ( n  = 374). Multivariate Cox analysis demonstrated that our PRLS model was an independent risk factor. More importantly, this signature displayed a stable and accurate performance in predicting prognosis at 1, 3, and 5 years, with all AUCs above 0.7. The decision curve analysis also indicated that our signature had promising clinical application. In addition, patients with high PRLS score suggested a more abundant immune infiltration, higher expression of immune checkpoint genes, and better response to immunotherapy but worse to chemotherapy. Conclusion: A novel pyroptosis-related lncRNA signature with a robust performance was constructed and validated in multiple cohorts. This signature provided new perspectives for clinical management and precise treatments of GBM.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-2-25)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-2-25)
    Abstract: Background: Recent evidence demonstrates that pyroptosis-derived long non-coding RNAs (lncRNAs) have profound impacts on the initiation, progression, and microenvironment of tumors. However, the roles of pyroptosis-derived lncRNAs (PDLs) in gastric cancer (GC) remain elusive. Methods: We comprehensively analyzed the multi-omics data of 839 GC patients from three independent cohorts. The previous gene set enrichment analysis embedding algorithm was utilized to identify PDLs. A gene pair pipeline was developed to facilitate clinical translation via qualitative relative expression orders. The LASSO algorithm was used to construct and validate a pyroptosis-derived lncRNA pair prognostics signature (PLPPS). The associations between PLPPS and multi-omics alteration, immune profile, and pharmacological landscape were further investigated. Results: A total of 350 PDLs and 61,075 PDL pairs in the training set were generated. Cox regression revealed 15 PDL pairs associated with overall survival, which were utilized to construct the PLPPS model via the LASSO algorithm. The high-risk group demonstrated adverse prognosis relative to the low-risk group. Remarkably, genomic analysis suggested that the lower tumor mutation burden and gene mutation frequency (e.g., TTN , MUC16 , and LRP1B ) were found in the high-risk group patients. The copy number variants were not significantly different between the two groups. Additionally, the high-risk group possessed lower immune cell infiltration abundance and might be resistant to a few chemotherapeutic drugs (including cisplatin, paclitaxel, and gemcitabine). Conclusion: PDLs were closely implicated in the biological process and prognosis of GC, and our PLPPS model could serve as a promising tool to advance prognostic management and personalized treatment of GC patients.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-7-29)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-7-29)
    Abstract: A considerable number of patients with stage II/III colorectal cancer (CRC) will relapse within 5 years after surgery, which is a leading cause of death in early-stage CRC. The current TNM stage system is limited due to the heterogeneous clinical outcomes displayed in patients of same stage. Therefore, searching for a novel tool to identify patients at high recurrence-risk for improving post-operative individual management is an urgent need. Methods Using four independent public cohorts and qRT-PCR data from 66 tissues, we developed and validated a recurrence-associated immune signature (RAIS) based on global immune genes. The clinical and molecular features, tumor immune microenvironment landscape, and immune checkpoints profiles of RAIS were also investigated. Results In five independent cohorts, this novel scoring system was proven to be an independent recurrent factor and displayed excellent discrimination and calibration in predicting the recurrence-risk at 1~5 years. Further analysis revealed that the high-risk group displayed high mutation rate of TP53, while the low-risk group had more abundance of activated CD4+/CD8+ T cells and high expression of PD-1/PD-L1. Conclusions The RAIS model is highly predictive of recurrence in patients with stage II/III CRC, which might serve as a powerful tool to further optimize decision-making in adjuvant chemotherapy and immunotherapy, as well as tailor surveillance protocol for individual patients.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 9
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-9-13)
    Abstract: Fecal microbiome transplantation (FMT) from healthy donors is one of the techniques for restoration of the dysbiotic gut, which is increasingly being used to treat various diseases. Notably, mounting evidence in recent years revealed that FMT has made a breakthrough in the oncology treatment area, especially by improving immunotherapy efficacy to achieve antitumor effects. However, the mechanism of FMT in enhancing antitumor effects of immune checkpoint blockers (ICBs) has not yet been fully elucidated. This review systematically summarizes the role of microbes and their metabolites in the regulation of tumor immunity. We highlight the mechanism of action of FMT in the treatment of refractory tumors as well as in improving the efficacy of immunotherapy. Furthermore, we summarize ongoing clinical trials combining FMT with immunotherapy and further focus on refined protocols for the practice of FMT in cancer treatment, which could guide future directions and priorities of FMT scientific development.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-11-29)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-11-29)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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