Yujie Xu, Zhicheng Lai, Anna Kan, Hui Liu, Yu Huang, Yueyuan Lai, Jiefeng Weng, Zhao-Feng Wu, Ming Shi, Wei-Li Gu, Shuai Zhang, Minke He
Background : The tumour mutation burden (TMB) is a valuable indicator of the accumulation of somatic mutations, and is thought to be associated with the biological behaviour and prognosis of tumours. However, the related genetic mechanism for these association is still unclear. The aim of the present study was to identify the key gene(s) associated with TMB in hepatocellular carcinoma (HCC) and to investigate its biological functions, downstream transcription factors, and mechanism of action. Methods : Patients in The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database were classified according to TMB signature-related genes. Key genes related to the TMB signature and tumour prognosis were identified. Immunohistochemistry and Quantitative Real-Time Polymerase Chain Reaction (qPCR) were then used to assess gene expression in clinical HCC tissues and HCC cells. Cells with altered gene expression were evaluated for the effect on cell proliferation and apoptosis, both in vitro and in vivo . Three independent databases and cell sequencing data were used to identify the mechanisms involved and the downstream transcription factors. The mechanism was also studied by altering the expression of downstream transcription factors in vitro . Result : The integrated cluster (IC) 2 group, characterized by 99 TMB signature-related genes, showed a significant different TMB score compared to the IC1 group ( p < 0.001), as well as more favourable tumour prognosis ( p = 0.031). We identified five key prognostic genes that were differentially expressed between IC2 and IC1 and were associated with overall survival. The expression of one of these key prognostic genes, RCAN2 , was negatively correlated with TMB in 18 out of 33 tumour types examined. A high level of RCAN2 was correlated with better overall survival in HCC ( p = 0.0009). Overexpression of RCAN2 enhanced apoptosis in vitro and in vivo , whereas knockdown of RCAN2 attenuated apoptosis. The mechanism by which RCAN2 promotes apoptosis may involve upregulation of the expression of ETS homologous factor ( EHF ) and of death receptor 5 ( DR5 ). Conclusions : Downregulation of RCAN2 expression was found to correlate with elevated TMB in multiple cancer types. RCAN2 was also found to be a biomarker of HCC prognosis, and to promote the apoptosis of HCC cells through the EHF/DR5 pathway. These findings provide a new perspective on systemic treatment for advanced HCC with a high TMB.
{"title":"TMB Signature-Related RCAN2 Promotes Apoptosis by Upregulating EHF/DR5 Pathway in Hepatocellular Carcinoma","authors":"Yujie Xu, Zhicheng Lai, Anna Kan, Hui Liu, Yu Huang, Yueyuan Lai, Jiefeng Weng, Zhao-Feng Wu, Ming Shi, Wei-Li Gu, Shuai Zhang, Minke He","doi":"10.31083/j.fbl2907243","DOIUrl":"https://doi.org/10.31083/j.fbl2907243","url":null,"abstract":"Background : The tumour mutation burden (TMB) is a valuable indicator of the accumulation of somatic mutations, and is thought to be associated with the biological behaviour and prognosis of tumours. However, the related genetic mechanism for these association is still unclear. The aim of the present study was to identify the key gene(s) associated with TMB in hepatocellular carcinoma (HCC) and to investigate its biological functions, downstream transcription factors, and mechanism of action. Methods : Patients in The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database were classified according to TMB signature-related genes. Key genes related to the TMB signature and tumour prognosis were identified. Immunohistochemistry and Quantitative Real-Time Polymerase Chain Reaction (qPCR) were then used to assess gene expression in clinical HCC tissues and HCC cells. Cells with altered gene expression were evaluated for the effect on cell proliferation and apoptosis, both in vitro and in vivo . Three independent databases and cell sequencing data were used to identify the mechanisms involved and the downstream transcription factors. The mechanism was also studied by altering the expression of downstream transcription factors in vitro . Result : The integrated cluster (IC) 2 group, characterized by 99 TMB signature-related genes, showed a significant different TMB score compared to the IC1 group ( p < 0.001), as well as more favourable tumour prognosis ( p = 0.031). We identified five key prognostic genes that were differentially expressed between IC2 and IC1 and were associated with overall survival. The expression of one of these key prognostic genes, RCAN2 , was negatively correlated with TMB in 18 out of 33 tumour types examined. A high level of RCAN2 was correlated with better overall survival in HCC ( p = 0.0009). Overexpression of RCAN2 enhanced apoptosis in vitro and in vivo , whereas knockdown of RCAN2 attenuated apoptosis. The mechanism by which RCAN2 promotes apoptosis may involve upregulation of the expression of ETS homologous factor ( EHF ) and of death receptor 5 ( DR5 ). Conclusions : Downregulation of RCAN2 expression was found to correlate with elevated TMB in multiple cancer types. RCAN2 was also found to be a biomarker of HCC prognosis, and to promote the apoptosis of HCC cells through the EHF/DR5 pathway. These findings provide a new perspective on systemic treatment for advanced HCC with a high TMB.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141685817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dynamics of Open States and Promoter Functioning in the appY_red and appY_green Genetic Constructions Based on the pPF1 Plasmid","authors":"Irina Masulis, Andrey Grinevich, Ludmila Yakushevich","doi":"10.31083/j.fbl2904155","DOIUrl":"https://doi.org/10.31083/j.fbl2904155","url":null,"abstract":"","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140685193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael R. Odom, Francis M Hughes Jr, NiQuava Pope, Huixia Jin, J. Purves
{"title":"Female Type 1 Diabetic Akita Mice Demonstrate Increased Bladder Contractility via FP Receptor Activation due to NLRP3-Mediated Inflammation","authors":"Michael R. Odom, Francis M Hughes Jr, NiQuava Pope, Huixia Jin, J. Purves","doi":"10.31083/j.fbl2904154","DOIUrl":"https://doi.org/10.31083/j.fbl2904154","url":null,"abstract":"","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140688909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Žarković, A. Gęgotek, W. Łuczaj, Morana Jaganjac, S. B. Šunjić, K. Žarković, Elżbieta Skrzydlewska
{"title":"Overview of the Lipid Peroxidation Measurements in Patients by the Enzyme-Linked Immunosorbent Assay Specific for the 4-Hydroxynonenal-Protein Adducts (4-HNE-ELISA)","authors":"N. Žarković, A. Gęgotek, W. Łuczaj, Morana Jaganjac, S. B. Šunjić, K. Žarković, Elżbieta Skrzydlewska","doi":"10.31083/j.fbl2904153","DOIUrl":"https://doi.org/10.31083/j.fbl2904153","url":null,"abstract":"","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140688946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metastasis and the Microbiome: The Impact of Bacteria in Disseminated Colorectal Cancer","authors":"Reed I. Ayabe, Michael G. White","doi":"10.31083/j.fbl2904152","DOIUrl":"https://doi.org/10.31083/j.fbl2904152","url":null,"abstract":"","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140689645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mikhail P. Vasilik, Natalia I. Belova, E. M. Lazareva, N. Kononenko, Larisa I. Fedoreyeva
{"title":"Salt Tolerance Assessment in Triticum Aestivum and Triticum Durum","authors":"Mikhail P. Vasilik, Natalia I. Belova, E. M. Lazareva, N. Kononenko, Larisa I. Fedoreyeva","doi":"10.31083/j.fbl2904150","DOIUrl":"https://doi.org/10.31083/j.fbl2904150","url":null,"abstract":"","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140709710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuxing Chen, Chaoyu Xiao, Qingxin Fan, Ye Zhang, Qiu Huang, Yunsheng Ou
Background : The extracellular matrix (ECM) modeling induced by the metalloproteinases is a vital characteristic for tumor progression. Previous studies mainly focus on the functions of two subgroups of metalloproteinases: matrix metalloproteinases (MMPs) and a disintegrin and metalloproteases (ADAMs) in tumors. The roles of another important group: the ADAMs with thrombospondin motifs (ADAMTS) remain unclear. This study aimed to perform a pan-cancer analysis of procollagen N-propeptidase subgroup of ADAMTS (PNPSA). Methods : We systematically analyzed expression landscape, genomic variations, prognostic value
{"title":"Multi-Omics Pan-Cancer Analysis of Procollagen N-Propeptidase Gene Family of ADAMTS as Novel Biomarkers to Associate with Prognosis, Tumor Immune Microenvironment, Signaling Pathways, and Drug Sensitivities","authors":"Yuxing Chen, Chaoyu Xiao, Qingxin Fan, Ye Zhang, Qiu Huang, Yunsheng Ou","doi":"10.31083/j.fbl2904151","DOIUrl":"https://doi.org/10.31083/j.fbl2904151","url":null,"abstract":"Background : The extracellular matrix (ECM) modeling induced by the metalloproteinases is a vital characteristic for tumor progression. Previous studies mainly focus on the functions of two subgroups of metalloproteinases: matrix metalloproteinases (MMPs) and a disintegrin and metalloproteases (ADAMs) in tumors. The roles of another important group: the ADAMs with thrombospondin motifs (ADAMTS) remain unclear. This study aimed to perform a pan-cancer analysis of procollagen N-propeptidase subgroup of ADAMTS (PNPSA). Methods : We systematically analyzed expression landscape, genomic variations, prognostic value","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140709253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tariq Aziz, M. Naveed, M. A. Shabbir, A. Sarwar, Ayaz Ali Khan, Ammarah Hasnain, Taqweem Ul Haq, Zhennai Yang, A. Zinedine, João Miguel Rocha, M. Alharbi
{"title":"Whole Genome Analysis of Tibetan Kefir-Derived Lactiplantibacillus Plantarum 12-3 Elucidates Its Genomic Architecture, Antimicrobial and Drug Resistance, Potential Probiotic Functionality and Safety","authors":"Tariq Aziz, M. Naveed, M. A. Shabbir, A. Sarwar, Ayaz Ali Khan, Ammarah Hasnain, Taqweem Ul Haq, Zhennai Yang, A. Zinedine, João Miguel Rocha, M. Alharbi","doi":"10.31083/j.fbl2904147","DOIUrl":"https://doi.org/10.31083/j.fbl2904147","url":null,"abstract":"","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140714646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhengze Sun, Haolan Ji, Yifan Zhou, H. Duan, B. Ma, H. Qi
{"title":"Profiles, Distribution, and Functions of Gamma Delta T Cells in Ocular Surface Homeostasis and Diseases","authors":"Zhengze Sun, Haolan Ji, Yifan Zhou, H. Duan, B. Ma, H. Qi","doi":"10.31083/j.fbl2904146","DOIUrl":"https://doi.org/10.31083/j.fbl2904146","url":null,"abstract":"","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140713117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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