检索结果-南通市图书馆

Benefit-Risk Assessment of Chinese Medicine Injections for Primary Liver cancer Based on Multi-criteria Decision Analysis

引用

Chinese Journal of Integrative Medicine 2024年第6期30卷 559-564页

作者： ZHANG Rong-rong SHAO Ming-yi FU Yu ZHAO Rui-xia WANG Jing-wen FANG Yu-xuan The First Clinical Medical College of henan university of Traditional Chinese Medicine Zhengzhou450046China Personal Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Scientific Research Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China Digestive Department the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou450000China

ObjectiveTo evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical *** controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation *** total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (−0.86, 17.75), 5 (−5.01, 11.09), and 6 (−1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, *** on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

关键词： multi-criteria decision analysis benefit-risk assessment Chinese medicine injections primary livercancer

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase(G6PD)by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis

引用

Science China(Life Sciences) 2024年第8期67卷 1648-1665页

作者： Jie Gao Xiaoyi Shi Yaohui Sun Xudong Liu Feng Zhang Chengcheng Shi Xiao Yu Zhiping Yan Long Liu Shizhe Yu Jiacheng Zhang Xiaodan Zhang Shuijun Zhang Wenzhi Guo Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China henan Diagnosis&Treatment League for Hepatopathy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China henan Innovative Research Group for Hepatobiliary&Pancreatic Surgery and Digestive Organ Transplantation Zhengzhou 450052China henan Organ Transplantation Quality Control Centre Zhengzhou 450052China henan Engineering Technology Research Center for Organ Transplantation Zhengzhou 450052China Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of General Surgery Huashan HospitalFudan University Shanghai 200040China cancer Metastasis Institute Fudan UniversityShanghai 200040China

Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely ***,we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma(HCC)using tissue samples from 198 *** was to be frequently found(86.6%)expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with *** overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo,whereas complete knockout of Bhmt(Bhmt^(−/−))produced the opposite *** combined proteomics,metabolomics,and molecular biological strategies and detected that Bhmt^(−/−)promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase(G6PD)and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing *** contrast,restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated ***,coimmunoprecipitation identified monomethylated modifications of the G6PD,and BHMT regulated the methylation of *** sequence analysis,generation and application of specific antibodies,and site-directed mutagenesis indicated G6PD methylation at the arginine residue ***,we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD,thereby inhibiting G6PD activity,which in turn suppressed *** together,this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency,suggesting a potential therapeutic strategy for HCC treatment.

关键词： HCC BHMT arginine methylation G6PD PPP metabolism

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks

引用

Science China(Life Sciences) 2024年第1期67卷 132-148页

作者： Ming Zhang Xiaoyang Wang Nan Yang Xu Zhu Zequn Lu Yimin Cai Bin Li Ying Zhu Xiangpan Li Yongchang Wei Shaokai Zhang Jianbo Tian Xiaoping Miao Department of Epidemiology and Biostatistics School of Public HealthDepartment of Gastrointestinal OncologyZhongnan Hospital of Wuhan UniversityDepartment of Radiation OncologyRenmin Hospital of Wuhan UniversityTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430071China Research Center of Public Health Renmin hospital of Wuhan UniversityWuhan UniversityWuhan 430060China Department of cancer Epidemiology The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalHenan Engineering Research Center of Cancer Prevention and ControlHenan International Joint Laboratory of Cancer PreventionZhengzhou 450008China Department of Gastrointestinal Surgery Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Radiation Oncology Renmin Hospital of Wuhan UniversityWuhan 430060China Department of Gastrointestinal Oncology Hubei Cancer Clinical Study CenterZhongnan Hospital of Wuhan UniversityWuhan 430062China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430073China Jiangsu Collaborative Innovation Center for cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China

Genome-wide association studies(GWASs)have identified over 140 colorectal cancer(CRC)-associated loci;however,target genes at the majority of loci and underlying molecular mechanisms are poorly ***,we utilized a Bayesian approach,integrative risk gene selector(iRIGS),to prioritize risk genes at CRC GWAS loci by integrating multi-omics *** a result,a total of 105 high-confidence risk genes(HRGs)were identified,which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in *** the 105 HRGs,CEBPB,located at the 20q13.13 locus,acted as a transcription factor playing critical roles in *** subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK,PI3K-Akt,and Ras ***,by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls,we elucidated that rs1810503,a putative functional variant regulating CEBPB,was associated with CRC risk(OR=0.90,95%CI=0.86–0.93,P=1.07×10^(−7)).The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 ***,the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via longrange promoter-enhancer interactions,mediated by the transcription factor,REST,and thus decreased CRC *** summary,our study provides a genetic resource and a generalizable strategy for CRC etiology investigation,and highlights the biological implications of CEBPB in CRC tumorigenesis,shedding new light on the etiology of CRC.

关键词： susceptibility genes gene screening models multi-omics GWAS CEBPB long-range promoter-enhancer interactions

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Implications of T cell-mediated tumor killing genes for molecular heterogeneity and clinical stratification in lung adenocarcinoma

引用

Genes & Diseases 2024年第4期11卷 39-41页

作者： Tong Qiao Beining Yin Jun Liang Li Wei Department of Thoracic Surgery Henan Provincial People's HospitalZhengzhouHenan 450000China Reproductive Medicine Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Breast Surgery Henan Provincial People's HospitalZhengzhouHenan 450000China

Due to the profound heterogeneity exhibited amongst patients with lung adenocarcinoma(LUAD),considerable variances in clinical efficacy emerge.1 For the aims of precision medicine,a clinical instrument to delineate distinct disease phenotypes and anticipate susceptibility to intervention is *** cytotoxicity mediated through T lymphocytes constitutes a pivotal mechanism of anti-tumoral immunity and the foundation for cancer immunotherapy.?Numerous genes regulating the sensitivity of tumor cells to killing mediated by T lymphocytes(GSTKKs)are conducive to satisfying the aforesaid medical necessity.

关键词： clinical mediated adenocarcinoma

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Protein translation:biological processes and therapeutic strategies for human diseases

引用

Signal Transduction and Targeted Therapy 2024年第3期9卷 1048-1064页

作者： Xuechao Jia Xinyu He Chuntian Huang Jian Li Zigang Dong Kangdong Liu Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan 450000China China-US(henan)Hormel cancer Institute ZhengzhouHenan 450000China Department of Pathology and Pathophysiology Henan University of Chinese MedicineZhengzhouHenan 450000China Tianjian Laboratory of Advanced Biomedical Sciences ZhengzhouHenan 450052China Research Center for Basic Medicine Sciences Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052 HenanChina Provincial Cooperative Innovation Center for cancer Chemoprevention Zhengzhou UniversityZhengzhouHenan 450000China State Key Laboratory of Esophageal cancer Prevention and Treatment Zhengzhou UniversityZhengzhouHenan 450000China The Collaborative Innovation Center of henan Province for cancer Chemoprevention ZhengzhouHenan 450000China

Protein translation is a tightly regulated cellular process that is essential for gene expression and protein *** deregulation of this process is increasingly recognized as a critical factor in the pathogenesis of various human *** this review,we discuss how deregulated translation can lead to aberrant protein synthesis,altered cellular functions,and disease *** explore the key mechanisms contributing to the deregulation of protein translation,including functional alterations in translation factors,tRNA,mRNA,and ribosome *** translation leads to abnormal protein expression,disrupted cellular signaling,and perturbed cellular functions-all of which contribute to disease *** development of ribosome profiling techniques along with mass spectrometry-based proteomics,mRNA sequencing and single-cell approaches have opened new avenues for detecting diseases related to translation ***,we highlight recent advances in therapies targeting translation-related disorders and their potential applications in neurodegenerative diseases,cancer,infectious diseases,and cardiovascular ***,the growing interest lies in targeted therapies aimed at restoring precise control over translation in diseased cells is *** conclusion,this comprehensive review underscores the critical role of protein translation in disease and its potential as a therapeutic *** in understanding the molecular mechanisms of protein translation deregulation,coupled with the development of targeted therapies,offer promising avenues for improving disease outcomes in various human ***,it will unlock doors to the possibility of precision medicine by offering personalized therapies and a deeper understanding of the molecular underpinnings of diseases in the future.

关键词： translation offering precise

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Shuxuening Injection Inhibits Apoptosis and Reduces Myocardial Ischemia-Reperfusion Injury in Rats through PI3K/AKT Pathway

引用

Chinese Journal of Integrative Medicine 2024年第5期30卷 421-432页

作者： YUE Tong-tong CAO Ying-jie CAO Ya-xuan LI Wei-xia WANG Xiao-yan SI Chun-ying XIA Han ZHU Ming-jun TANG Jin-fa WANG He The First Clinical Medical College of henan university of Chinese Medicine Zhengzhou 450046China Department of Pharmacy the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 451200China Department of Cardiovascular Diseases the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 451200China

Objective: To investigate the main components and potential mechanism of Shuxuening Injection(SXNI) in the treatment of myocardial ischemia-reperfusion injury(MIRI) through network pharmacology and in vivo research. Methods: The Traditional Chinese Medicine Systems Pharmacology(TCMSP) and Pharm Mapper databases were used to extract and evaluate the effective components of Ginkgo biloba leaves, the main component of SXNI. The Online Mendelian Inheritance in Man(OMIM) and Gene Cards databases were searched for disease targets and obtain the drug target and disease target intersections. The active ingredient-target network was built using Cytoscape 3.9.1 software. The STRING database, Metascape online platform, and R language were used to obtain the key targets and signaling pathways of the anti-MIRI effects of SXNI. In order to verify the therapeutic effect of different concentrations of SXNI on MIRI in rats, 60 rats were first divided into 5 groups according to random number table method: the sham operation group, the model group, SXNI low-dose(3.68 mg/kg), medium-dose(7.35 mg/kg), and high-dose(14.7 mg/kg) groups, with 12 rats in each group. Then, another 60 rats were randomly divided into 5 groups: the sham operation group, the model group, SXNI group(14.7 mg/kg), SXNI+LY294002 group,and LY294002 group, with 12 rats in each group. The drug was then administered intraperitoneally at body weight for 14 days. The main biological processes were validated using in vivo testing. Evans blue/triphenyltetrazolium chloride(TTC) double staining, hematoxylin-eosin(HE) staining, terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) assay, enzyme-linked immunosorbent assay(ELISA), and Western blot analysis were used to investigate the efficacy and mechanism of SXNI in MIRI rats. Results: Eleven core targets and 30 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways were selected. Among these, the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) pathway was

关键词： myocardial ischemia reperfusion injury PI3K/AKT signaling pathway Shuxuening Injection apoptosis Ginkgo biloba leaves

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

miR-30a-5p/PHTF2 axis regulates the tumorigenesis and metastasis of lung adenocarcinoma

引用

BIOCELL 2024年第4期48卷 581-590页

作者： LIJUAN ZHANG QINGYIN MENG LI ZHUANG QUAN GONG XIANDA HUANG XUEQIN LI SHIJUAN LI GUOQIN WANG XICAI WANG Department of Rehabilitation and Palliative Medicine The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of Pathology The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Emergency Department(Outpatient Chemotherapy Center) The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of cancer BioTreatment Center The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina Department of cancer Institute The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalKunmingChina

Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective *** this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung ***:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal *** experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma ***,we examined tumorigenesis and metastasis in a nude mouse ***:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma *** of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant ***,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal ***,PHTF2 was found to be a molecular target of *** PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p ***:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung ***,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.

关键词： Lung cancer Malignant phenotype Tumor formation Tumor suppressor Oncogene

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Repressing iron overload ameliorates central poststroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke

引用

Neural Regeneration Research 2024年第12期19卷 2708-2722页

作者： He Fang Mengjie Li Jingchen Yang Shunping Ma Li Zhang Hongqi Yang Qiongyan Tang Jing Cao Weimin Yang Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Nutrition The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Neurology Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Department of Human Anatomy School of Basic Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Neuroscience Research Institute Zhengzhou University Academy of Medical SciencesZhengzhouHenan ProvinceChina

Thalamic hemorrhage can lead to the development of central post-stroke *** in histone acetylation levels,which are regulated by histone deacetylases,affect the excitability of neurons surrounding the hemorrhagic ***,the regulato ry mechanism of histone deacetylases in central post-stroke pain remains unclea ***,we show that iron overload leads to an increase in histone deacetylase 2expression in damaged ventral posterolateral nucleus *** this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium(Kv)channel subunit gene in a rat model of central post-stroke pain,thereby increasing Kcna2expression and relieving central ***,in the absence of nerve injury,increasing histone deacetylase 2 expression decreased Kcna2expression,decreased Kv current,increased the excitability of neurons in the ventral posterolateral nucleus area,and led to neuropathic pain ***,treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage,reversed histone deacetylase 2 upregulation and Kv1.2 downregulation,and alleviated mechanical hypersensitivity in central post-stroke pain *** results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation,mediated by iron overload,are important factors in central post-stroke pain pathogenesis and co uld se rve as new to rgets for central poststroke pain treatment.

关键词： central post-stroke pain hemorrhagic stroke histone deacetylase iron overload voltage-gated potassium ion channel 1.2

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Co-alteration of Myc and RTK-RAS pathways defines a liver-metastatic propensity and immune-cold subgroup of pancreatic adenocarcinoma

引用

Genes & Diseases 2024年第3期11卷 47-50页

作者： Yuyuan Zhang Ziyang Zu Hui Xu Siyuan Weng Yuqing Ren Quan Cheng Peng Luo Jian Zhang Zaoqu Liu Xinwei Han Department of Interventional Radiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Interventional Institute of zhengzhou university ZhengzhouHenan450052China Interventional Treatment and Clinical Research Center of henan Province ZhengzhouHenan 450052China Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan450052China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Oncology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong 510280China

Co-altered pathways refer to the phenomenon where multiple biological pathways exhibit aberrant changes simultaneously within the same tumor *** phenomenon can facilitate a better understanding of the mechanism and evolution of tumors and serve as a biological marker for diagnosing,classifying,and treating tumors.1 However,the nature of alteration occurrence and the impact on pancreatic adenocarcinoma(PAAD)remain *** SELECT algorithm was originally designed to systematically assess the evolutionary dependencies and their impact between altered genes in cancer for anticipating drug resistance and proposing alternative ***,to better characterize the etiology of PAAD and develop an improved risk assessment strategy,2 by utilizing SELECT,we identified a co-altered pathway subgroup of PAAD that demonstrated an elevated risk for unfavorable prognosis,a propensity for liver metastasis,and an immunologically cold microenvironment.

关键词： adenocarcinoma elevated alteration

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma

引用

National Science Review 2024年第5期11卷 170-185页

作者： Yong Zhou Shanlan Mo Heyang Cui Ruifang Sun Weimin Zhang Xiaofei Zhuang Enwei Xu Hongyi Li Yikun Cheng Yongsheng Meng Meilin Liu Ting Yan Huijuan Liu Ling Zhang Bin Yang Yanfeng Xi Shubin Wang Xiaolong Cheng Shuai Cheng Li Zhihua Liu Qimin Zhan Zheng Hu Yongping Cui cancer Institute Department of Pathology Peking University Shenzhen Hospital Shenzhen Peking University-the Hong Kong University of Science and Technology(PKU-HKUST) Medical Center Institute of Cancer ResearchShenzhen Bay Laboratory Key Laboratory of Cellular Physiology of the Ministry of Education Department of Pathology Shanxi Medical University City university of Hong Kong Shenzhen Research Institute CAS Key Laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of Sciences Department of Surgery Faculty of Medicine The Chinese University of Hong Kong Department of Tumor Biobank Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital & Institute Research Unit of Molecular cancer Research Chinese Academy of Medical Sciences Department of Thoracic Surgery Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University Department of Pathology Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University College of Letters & Science University of California Berkeley State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

Esophageal squamous cell carcinoma（ESCC） is a poor-prognostic cancer type with extensive intra-and inter-patient heterogeneity in both genomic variations and tumor microenvironment（TME）. However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor PREX2,accounting for 22% of ESCCs with frequent somatic mutations or hyper-methylation, which promoted migration and invasion of ESCC cells in vitro. Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution, where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the ***, we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness, suggesting more stringent immune selection. In addition, distinct TMEs were associated with variable genomic and clinical outcomes. Among them, hot TME was associated with high immune evasion and subclonal heterogeneity. We also found that immunoediting, instead of CD8+T cell abundance, acts as an independent prognostic factor of ESCCs. Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted ***, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.

关键词： squamous cell carcinoma heterogeneity multi-omics evolution tumor microenvironment

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：