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The unique genomic landscape and prognostic mutational signature of Chinese clear cell renal cell carcinoma

Journal of the National Cancer Center 2022年第3期2卷 162-170页

作者： Wenhao Xu Aihetaimujiang Anwaier Wangrui Liu Xi Tian Jiaqi Su Guohai Shi Yuanyuan Qu Hailiang Zhang Dingwei Ye Department of Urology Fudan University Shanghai Cancer CenterShanghai Medical CollegeFudan UniversityShanghaiChina Department of Interventional Oncology Renji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Background:The genomic background affects the occurrence and metastasis of cancers,including clear cell renal cell carcinoma(ccRCC).However,reports focusing on the prognostic mutational signature of Chinese ccRCC are ***:Overall,929 patients,including a training cohort with Chinese patients(n=201),a testing cohort with Caucasian patients(n=274),and a validation cohort(n=454)were analyzed for the genomic landscape of ***,machine-learning algorithms were used to identify and evaluate the genomic mutational signature(GMS)in *** for prognosis,immune microenvironment,association with independent clinicopathological features,and predictive responses for immune checkpoint therapies(ICTs)were ***:The DNA variation data of 929 patients with ccRCC suggested markedly differential genomic mutational frequency of the most frequent genes,such as VHL,PBRM1,BAP1,SETD2,and KDM5C between the Chinese and Caucasian ***1 showed significant co-occurrence with VHL and *** then successfully iden-tified a seven-gene mutational signature(GMS^(Mut))that included mutations in FBN1,SHPRH,CELSR1,COL6A6,DST,ABCA13,and *** GMS^(Mut)significantly predicted progressive progression(P<0.0001,HR=2.81)and poor prognosis(P<0.0001,HR=3.89)in the Chinese training ***,ccRCC patients with the GMS^(Mut)had poor survival rates in the testing cohort(P=0.020)and poor outcomes were predicted for those treated with ICTs in the validation cohort(P=0.036).Interestingly,a favorable clinical response to ICTs,ele-vated expression of immune checkpoints,and increased abundance of tumor-infiltrated lymphocytes,specifically CD8^(+)T cells,Tregs,and macrophages,were observed in the GMS^(Mut)***:This study described the pro-tumorigenic GMS^(Mut)cluster that improved the prognostic accuracy in Chinese patients with *** discovery of the novel independent prognostic signature highlights the relationship between tumor phenotype a

关键词： Clear cell renal cell carcinoma genomic mutation Immune checkpoint therapies Prognosis Tumor microenvironment

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Shared-probe system:An accurate,low-cost and general enzyme-assisted DNA probe system for detection of genetic mutation

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Chinese Chemical Letters 2022年第6期33卷 3043-3048页

作者： Lida Ren Zhihao Ming Wei Zhang Yangwei Liao Xiaofeng Tang Bei Yan Huimin Lv Xianjin Xiao Centre of Reproductive Medicine/Family Planning Research Institute Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Obstetrics and Gynecology Third Hospital of Shanxi Medical University.Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalTongji Medical College.Huazhong University of Science and TechnologyTaiyuan 030032China

Enzyme assisted DNA probes are powerful tools in molecular diagnostics for their simplicity,rapidity,and low detection ***,cost of probes,difficulty in optimization and disturbance of secondary structure hindered the wider application of enzyme assisted DNA *** solve the problems,we designed a new system named shared-probe *** introducing two unlabeled single stranded DNA named Sh1 and Sh2 as the bridge between probe and the substrate,the same sequence of dually labeled probe with stable performance was shared for different mutations,thus sparing the expense and time cost on designing,synthesizing and optimizing corresponding ***,the hybridization between Sh1 and the substrate could overcome secondary structures,which guaranteed the detection of different *** performance and generality of the design were tested by low abundance detection in synthetic single DNA samples and the limit of detection was 0.05%for PTENR130 Q,EGFR-L858 R and 0.02%for *** genomic DNA samples,the limit of detection of 0.1%can be achieved for EGFR-L858 R,demonstrating the potential of clinical application in our design.

关键词： Nucleic acid probe EndonucleaseⅣ Secondary structure genomic mutation SNP detection

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