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Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on UK Biobank data

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cancer Biology & Medicine 2024年第8期21卷 712-723页

作者： Yu Zhang Chao Sheng Zhangyan Lyu Hongji Dai Fangfang Song Fengju Song Yubei Huang Kexin Chen Department of Epidemiology and Biostatistics Key Laboratory of Molecular Cancer EpidemiologyKey Laboratory of Prevention and Control of Human Major DiseasesMinistry of EducationNational Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin Medical UniversityTianjin 300060China

Objective: Few studies have evaluated the benefits of colorectal cancer(CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model(Qcancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and ***: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios(HRs) and absolute risk reductions(ARRs) for CRC incidence and mortality according to risk ***: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediateand high-risk groups [incidence: HR: 0.87, 95% confidence interval(CI): 0.81±0.94;0.81, 0.73±0.90;mortality: 0.75, 0.64±0.87;0.70, 0.58±0.85], which composed approximately 60% of the study population. The ARRs(95% CI) were 0.17(0.11±0.24) and 0.43(0.24±0.61), respectively, for CRC incidence, and 0.08(0.05±0.11) and 0.24(0.15±0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk ***: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.

关键词： Colorectal cancer screening polygenic risk score incidence mortality

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

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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

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Global burden of thyroid cancer in 2022:Incidence and mortality estimates from GLOBOCAN

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Chinese Medical Journal 2024年第21期137卷 2567-2576页

作者： Zhangyan Lyu Yu Zhang Chao Sheng Yubei Huang Qiang Zhang Kexin Chen Department of Epidemiology and Biostatistics Key Laboratory of Molecular Cancer EpidemiologyKey Laboratory of Prevention and Control of Human Major DiseasesMinistry of EducationNational Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin Medical UniversityTianjin 300060China Department of Maxillofacial and Otorhinolaryngology Oncology National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin Medical University Cancer Institute and HospitalTianjin 300060China

Background:Thyroid cancer(TC)is the most common malignancy of the endocrine *** study aimed to assess the global distribution of TC incidence and mortality in 2022,as well as to predict the burden for the year ***:Data from the GLOBOCAN 2022 database were used to analyze the age-standardized incidence and mortality rates of TC by sex,age group(<55 years and≥55 years),country,world region,and level of Human Development Index(HDI)for 185 *** predicted incidence and mortality burden for 2050 was calculated based on demographic ***:In 2022,an estimated 821,214 new TC cases and 47,507 TC-related deaths occurred *** age-standardized incidence rates(ASIRs)and age-standardized mortality rates(ASMRs)were higher in women(ASIR:13.60 per 100,000;ASMR:0.53 per 100,000)than in men(ASIR:4.60 per 100,000;ASMR:0.35 per 100,000).The ASIR in high HDI countries was approximately ten times higher than that in low HDI countries for both sexes,with relatively similar ASMR across *** 185 countries,China had the largest number of TC cases(accounting for 56.77% of total cases)and TC-related deaths(accounting for 24.35% of global TC-related deaths),with the highest ASIR in men(13.30 per 100,000).Worldwide,approximately 64.63% of TC cases occurred in populations under 55 years old,while nearly 82.99% of TC-related deaths occurred in populations aged 55 years and *** the rates stay the same as in 2022,it is projected that approximately 1,100,000 new TC cases and 91,000 TC-related deaths will occur in 2050,indicating a 34.15% and 89.58% increase,***:TC is a highly frequent cancer worldwide with disparities across regions,genders,and age *** results provide light on the worldwide TC disease burden and facilitate regionally customized prevention measures.

关键词： Thyroid cancer Incidence Mortality Trend analysis GLOBOCAN 2022

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Circulating tumor DNA as prognostic markers of relapsed breast cancer:a systematic review and meta-analysis

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Journal of the National cancer Center 2024年第1期4卷 63-73页

作者： Na’na Guo Qingxin Zhou Xiaowei Chen Baoqi Zeng Shanshan Wu Hongmei Zeng Feng Sun Hebei Province Centers for Disease Control and Prevention ShijiazhuangChina Tianjin Centers for Disease Control and Prevention TianjinChina Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijingChina Department of Science and Education Peking University Binhai HospitalTianjinChina Clinical Epidemiology and EBM Unit National Clinical Research Center for Digestive DiseasesBeijing Friendship HospitalCapital Medical UniversityBeijingChina National Central Cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Key Laboratory of Major Disease Epidemiology Ministry of Education(Peking University)BeijingChina

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical *** were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies;(2) patients with breast cancer;(3) ctDNA measurement;(4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate. Results: A total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50–0.83), with lower ORR in the ctDNA-positive group than ctDNAnegative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04–0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR]

关键词： ctDNA Breast cancer Prognostic outcome prediction Meta-analysis

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Physical activity and risk of lung cancer:A systematic review and dose-response meta-analysis of cohort studies

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Journal of the National cancer Center 2023年第1期3卷 48-55页

作者： Ranran Qie Minghui Han Huang Huang Peiyuan Sun Yuting Xie Jie He Yawei Zhang Department of Cancer Prevention and Control National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Epidemiology and Biostatistics School of Public HealthNanjing Medical UniversityNanjingChina National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Objective:To synthesize the knowledge about the association of total physical activity(TPA),leisure-time phys-ical activity(LTPA),occupational physical activity(OPA)and lung cancer risk and explore the dose-response relationship between LTPA level and lung ***:PubMed and Web of Science were searched up to 17 November *** summary relative risks(RRs)and 95%confidence intervals(CIs)were calculated by random-effects or fixed-effects *** dose-response analysis was conducted with restricted cubic ***:We identified 25 articles(42 cohort studies)that assessed the physical activity-lung cancer association,including 9,983,295 study participants and 85,988 incident cases of lung *** comparing the highest to the lowest level of TPA and LTPA,lung cancer risk reduced 22%(RR,0.78;95%CI:0.70,0.86)and 12%(RR,0.88;95%CI:0.83,0.93),*** found an approximately U-shaped association between LTPA and lung cancer(P non-linearity<0.001),with the lowest risk at 15 metabolic equivalent of task hours per week(h/wk)of *** to participants with sitting occupations,lung cancer risk significantly increased among those being unemployed(RR,1.33;95%CI:1.17,1.51)or with standing occupations(RR,1.37;95%CI:1.15,1.63),but not among those with light or high ***:Our meta-analysis supported a protective effect of TPA and LTPA,but not OPA,on lung cancer *** novel finding of a U-shaped association between LTPA and lung cancer risk warrants further investigation.

关键词： Cohort studies Dose-response Meta-analysis Physical activity Lung cancer

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Quantile Differences in the Age-Related Decline in Cardiorespiratory Fitness Between Sexes in Adults Without Type 2 Diabetes Mellitus in the United States

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Mayo Clinic Proceedings: Innovations, Quality and Outcomes 2022年第4期6卷 302-310页

作者： Ortaglia, Andrew Stansbury, Melissa L. Wirth, Michael D. Sui, Xuemei Bottai, Matteo Department of Epidemiology and Biostatistics Arnold School of Public Health University of South Carolina Columbia SC Department of Exercise Science Arnold School of Public Health University of South Carolina Columbia SC College of Nursing and Department of Epidemiology and Biostatistics Cancer Prevention and Control Program Arnold School of Public Health University of South Carolina Columbia SC Division of Biostatistics Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

Objective: To comprehensively assess the extent to which the decline in cardiorespiratory fitness (CRF) with age differs between sexes. Participants and Methods: This study used data from the Aerobics Center Longitudinal Study, conducted between September 1974 and August 2006, consisting primarily of White adults from middle-to-upper socioeconomic strata restricted to adults without type 2 diabetes mellitus (33,742 men and 9,415 women). Quantile regression models were used to estimate the differences in age-associated changes in CRF between the sexes, estimated using a maximal treadmill test. Results: For adults aged up to 45 years, significant differences in slopes relating to age and CRF between men and women were observed for all adjusted percentiles of CRF other than the 90th percentile;women reported significantly greater declines in CRF per year. For those aged 45-60 years and those older than 60 years, no significant differences in age-related declines in CRF were observed between the sexes. Conclusion: This study found that compared with men, the onset of decline in CRF was found to occur earlier and at lower CRF percentiles in women. This is of particular concern, given that compared with men, women already tend to have lower CRF levels. These findings suggest that maintaining the levels of physical activity sufficient to maintain moderate-to-high levels of fitness is particularly important for women earlier during adulthood. © 2022 The Authors

关键词： CRF cardiorespiratory fitness NCD noncommunicable disease T2DM type 2 diabetes mellitus VO 2max maximal oxygen consumption

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Genetic Insights into Glycine’s Protective Role Against CAD—European and East Asia,2015 and 2020

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China CDC weekly 2024年第9期6卷 168-172,I0003-I0008页

作者： Jiaying Yu Zhuolin Zhu Ting Wang Yuanhao Wei Lianjie Huang Qianru Zhang Yuting Zhang Yiran Wang Guiyou Liu Xiang Shu Rennan Feng Department of Nutrition and Food Hygiene School of Public HealthHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina Key Laboratory of Precision Nutrition and Health of Ministry of Education School of Public HealthHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina Songyang County Center for Disease Prevention and Control Songyang CityZhejiang Province China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer CenterNew York CityNYUSA

Introduction:The purpose of this study is to examine the potential causal relationship between levels of circulating glycine and coronary artery disease(CAD)using a two-step Mendelian randomization(MR)***:We analyzed data from genome-wide association studies(GWAS)conducted on European and East Asian *** assess the causal effects of circulating glycine levels on the risk of *** used the inverse-variance weighting(IVW),weighted median(WM),MR-Egger,and Mendelian Randomization Pleiotropy RESidual Sum and Outlier(MR-PRESSO)***,we conducted mediation analysis to investigate the contribution of blood pressure and other cardiovascular disease-related ***:The two-step Mendelian randomization analysis revealed that higher levels of glycine in the blood were associated with a reduced risk of CAD in Europeans[odds ratio(OR)=0.84,95%confidence interval(CI):0.72,−0.98;P=0.029]and East Asians:(OR=0.76,95%CI:0.66,−0.89;P=3.57×10−4).Sensitivity analysis confirmed the robustness of these ***,our results suggest that about 6.06%of the observed causal effect is mediated through genetically predicted systolic blood pressure(SBP)in the European ***:Our results contribute to the current knowledge regarding the involvement of glycine in the progression of CAD,and provide valuable methodological insights for the prevention and treatment of this condition.

关键词： CAD prevention involvement

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The prognostic role of circulating tumor DNA across breast cancer molecular subtypes:A systematic review and meta-analysis

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Journal of the National cancer Center 2024年第2期4卷 153-161页

作者： Nana Guo Qingxin Zhou Meng Zhang Xiaowei Chen Baoqi Zeng Shanshan Wu Hongmei Zeng Mopei Wang Fei Ma Feng Sun Hebei Centers for Disease Control and Prevention ShijiazhuangChina Tianjin Centers for Disease Control and Prevention TianjinChina Department of Epidemiology and Biostatistics School of Public HealthPeking University Health Science CenterBeijingChina Department of Science and Education Peking University Binhai HospitalTianjinChina Clinical Epidemiology and EBM Unit National Clinical Research Center for Digestive DiseasesBeijing Friendship HospitalCapital Medical UniversityBeijingChina National Central Cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Radiation Oncology Peking University Third HospitalBeijingChina Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Key Laboratory of Major Disease Epidemiology Ministry of Education(Peking University)BeijingChina

Objective:Circulating tumor DNA(ctDNA)is increasingly being used as a potential prognostic biomarker in cancer *** aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment *** and methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical *** databases were searched from January 2016 to May *** following search terms were used:ctDNA OR circulating tumor DNA AND breast cancer OR breast *** studies written in English were *** following pre-specified criteria should be met for inclusion:(i)original articles,conference abstracts,etc.;(ii)patients with breast cancer;(iii)ctDNA measurement;and(iv)clinical outcome data such as recurrence-free survival(RFS)and overall survival(OS).The random-effects model was preferred considering the potential het-erogeneity across *** main outcomes are ctDNA detection rate and postoperative long-term outcomes(RFS and OS).Results:A total of 24 studies were *** every measurement time,the ctDNA detection rate of the HR+subgroup was similar to that of the HR-subgroup(P=0.075;P=0.458;P=0.744;and P=0.578),and the ctDNA detection rate of the HER2+subgroup was similar to that of the HER2-subgroup(P=0.805;P=0.271;P=0.807;and P=0.703).In the HR+subgroup,RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients(P=0.589 and P=0.110),while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR-subgroup(HR=4.03,P<0.001;HR=3.21,P<0.001).According to HER grouping,the results were the same as *** the triple negative breast cancer(TNBC)subgroup,the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after ***:ctDNA was more predictive of recurrence-free survival and overall survival in the HR-subgroup than in the HR+subgroup,and the same re

关键词： ctDNA Breast cancer Molecular subtype RFS OS

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Inflammation as a Mediator of Microbiome Dysbiosis-Associated DNA Methylation Changes in Gastric Premalignant Lesions

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Phenomics 2023年第5期3卷 496-501页

作者： Lingjun Yan Wanxin Li Fenglin Chen Junzhuo Wang Jianshun Chen Ying Chen Weimin Ye Department of Epidemiology and Health Statistics School of Public HealthFujian Medical UniversityFuzhou 350122China Key Laboratory of Ministry of Education for Gastrointestinal Cancer Fujian Medical UniversityFuzhou 350122China Department of Gastroenterology Fujian Medical University Union HospitalFuzhou 350001China Changle Center for Disease Prevention and Control Fuzhou 350200China Changle Institute for Cancer Research Fuzhou 350200China Department of Medical Epidemiology and Biostatistics Karolinska InstitutetStockholm 17177Sweden

Evidence for the influence of chronic inflammation induced by microbial dysbiosis on aberrant DNA methylation supports a plausible connexion between disordered microbiota and precancerous lesions of gastric cancer(PLGC).Here,a comprehensive study including multi-omics data was performed to estimate the relationships amongst the gastric microbiome,inflammatory proteins and DNA methylation alterations and their roles in PLGC *** results demonstrated that gastric dysbacteriosis increased the risk of PLGC and DNA methylation alterations in related tumour suppressor *** inflammatory biomarkers were identified for antrum and corpus tissues,respectively,amongst which the expression levels of several biomarkers were significantly correlated with the microbial dysbiosis index(MDI)and methylation status of specific tumour suppressor ***,mediation analysis revealed that microbial dysbiosis partially contributed to DNA methylation changes in the stomach via the inflammatory cytokines C-C motif chemokine 20(CCL20)and tumour necrosis factor receptor superfamily member 9(TNFRSF9).Overall,these results may provide new insights into the mechanisms that might link the gastric microbiome to PLGC.

关键词： Gastric premalignant lesions Microbiome dysbiosis Inflammation DNA methylation Mediation analysis

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The efficacies and biomarker investigations of antiprogrammed death-1 (anti-PD-1)-based therapies for metastatic bone and soft tissue sarcoma

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cancer Biology & Medicine 2022年第6期19卷 910-930页

作者： Jia Lu Ting Li Zhichao Liao Hui Yu Yongtian Zhao Haixiao Wu Zhiwu Ren Jun Zhao Ruwei Xing Sheng Teng Yun Yang Xiangchun Li Kexin Chen Jonathan Trent Jilong Yang Department of Bone and Soft Tissue Tumor Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Infection Management Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Key Laboratory of Molecular Cancer Epidemiology Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China YuceBio Technology Co. Ltd.Shenzhen 518172China Department of Epidemiology and Biostatistics Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Sarcoma Multidisciplinary Program Sylvester Comprehensive Cancer CenterThe University of MiamiMiamiFL 33136USA

Objective:Sarcomas are a group of rare malignancies with various *** with metastatic sarcoma who have failed traditional treatments can possibly achieve better prognoses from using novel therapies,including anti-programmed death-1(PD-1)-based ***:We retrospectively analyzed clinical data of 24 metastatic sarcoma patients from June 15,2016 to December 30,*** patients mainly received angiogenesis inhibitors combined with anti-PD-1 therapy after they became resistant to traditional ***,8 patients underwent panel DNA and whole transcript ***:Six patients received 2 cycles of anti-PD-1 therapy and were included in the safety evaluation only *** median follow-up time was 5.77 *** median progression-free survival was 7.59 months,the overall response rate was 16.7%and the disease control rate was 55.6%.Based on whole exome and transcript sequencing data,there was no association between TMB,TNB,MSI,HLA-LOH,and PD-L1 expressions and sarcoma types with clinical *** efficacy and bioinformatics analyses indicated higher intratumoral heterogeneity(ITH)in progressive disease(PD)patients and lower ITH in partial response(PR)and stable disease patients.A higher percentage of immune cell infiltration,especially monocytes,was observed in PR *** stromal gene expression was increased in PD patients but decreased in PR *** analysis revealed that an increased TGF-βsignaling pathway was reversely correlated with anti-PD-1 efficacy,while a decreased inflammatory response signaling pathway was positively correlated with anti-PD-1 ***:Our study showed PD-1 inhibitors combined with anti-angiogenesis agents were effective and ***,monocyte ratio,stroma subtypes,and the status of immune-associated signaling pathways may be related with anti-PD-1 based therapy.

关键词： Sarcoma PD-1 PD-L1 immunotherapy angiogenesis safety efficacy biomarker

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