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Evaluation of 30 DNA damage response and 6 mismatch repair gene mutations as biomarkers for immunotherapy outcomes across multiple solid tumor types
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作者 Zhe Gong Yue Yang +1 位作者 Jieyun Zhang Weijian Guo 《Cancer Biology & Medicine》 SCIE CAS CSCD 2021年第4期1080-1091,共12页
Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multip... Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published dataset.The Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study.Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the TMB.Single MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy. 展开更多
关键词 Immune checkpoint inhibitor therapy prediction of efficacy tumor mutation burden mismatch repair deficiency DNA damage response genes
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TMB相关免疫浸润调控评分(MOTIF)预测免疫治疗响应并指导联合增效
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作者 钱政宇 潘艺芊 +7 位作者 李薛鑫 陈衍行 吴灏祥 刘泽先 Martin Kosar Jiri Bartek 王梓贤 徐瑞华 《Science Bulletin》 SCIE EI CAS CSCD 2024年第6期803-822,共20页
Patients with high tumor mutational burden(TMB)levels do not consistently respond to immune checkpoint inhibitors(ICIs),possibly because a high TMB level does not necessarily result in adequate infiltration of CD8^(+)... Patients with high tumor mutational burden(TMB)levels do not consistently respond to immune checkpoint inhibitors(ICIs),possibly because a high TMB level does not necessarily result in adequate infiltration of CD8^(+)T cells.Using bulk ribonucleic acid sequencing(RNA-seq)data from 9311 tumor samples across 30 cancer types,we developed a novel tool called the modulator of TMB-associated immune infiltration(MOTIF),which comprises genes that can determine the extent of CD8^(+)T cell infiltration prompted by a certain TMB level.We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle.By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors,we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8^(+)T cell infiltration.Using pretreatment RNA-seq data from 13 ICI-treated cohorts,we validated the use of MOTIF in predicting CD8^(+)T cell infiltration and ICI efficacy.Among the components of MOTIF,we identified EMC3 as a negative regulator of CD8^(+)T cell infiltration,which was validated via in vivo studies.Additionally,MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8^(+)T cell infiltration and improve ICI efficacy. 展开更多
关键词 Tumor mutational burden Immunotherapy Cancer-immunity cycle Treatment efficacy prediction CD8^(+)T cell infiltration Combination therapy
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Predicting the 7^(th)Day Efficacy of Acupoint Application of Chinese Herbs(Xiao Zhong Zhi Tong Tie)in Patients with Diarrhea——A Machine-Learning Model Based on XGBoost Algorithm
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作者 Song Sheng Rui Li +3 位作者 Xing Wang Hong-Yang Gao Yan-Hong Zhang Feng-Qin Xu 《World Journal of Traditional Chinese Medicine》 CAS 2022年第2期257-261,共5页
Objective:Extreme gradient boosting(XGBoost)was used to predict the 7^(th)day efficacy of the acupoint application(AP)of Chinese herbs(Xiao Zhong Zhi Tong Tie)in patients with diarrhea.Materials and Methods:We consecu... Objective:Extreme gradient boosting(XGBoost)was used to predict the 7^(th)day efficacy of the acupoint application(AP)of Chinese herbs(Xiao Zhong Zhi Tong Tie)in patients with diarrhea.Materials and Methods:We consecutively collected medical records of patients with diarrhea nationwide on the Chun Bo Wan Xiang cloud platform from August 22 to November 5,2020.Demographic and clinical data and the fecal properties were included in this study.We established the XGBoost model to predict the 7^(th)day efficacy of AP in patients with diarrhea.The XGBoost model was evaluated using the area under the receiver operating characteristic(ROC)curve(AUC).We next compared the performance of XGBoost with that of artificial neural network(ANN),ANN+boosting,ANN+bagging,and support vector machine(SVM).Results:The XGBoost model provided a prediction accuracy of 84.86%(95%confidence interval=82.74%to 86.81%)and the ROC curve analysis showed an AUC of 0.81.The top-three variables with the highest importance are age,duration of diarrhea,and region(North).Our study revealed that XGBoost was not superior to ANN,ANN+boosting,ANN+bagging,and SVM.Conclusions:The established XGBoost model for predicting the 7^(th)day efficacy of AP in patients with diarrhea exhibited good accuracy and precision,which can be used for efficacy prediction. 展开更多
关键词 Acupoint application DIARRHEA efficacy prediction XGBoost Xiao Zhong Zhi Tong Tie
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