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Family history of esophageal cancer modifies the association of serum lipids and malignant esophageal lesions:a nested case-control study from the"Endoscopic Screening for Esophageal cancer in China"trial

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Chinese Medical Journal 2021年第9期134卷 1079-1086页

作者： Min-Min Wang Chuan-Hai Guo Feng-Lei Li Rui-Ping Xu Zhen Liu Ya-Qi Pan Fang-Fang Liu Ying Liu Hong Cai Meng-Fei Liu Zhong-Hu He Yang Ke Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of GeneticsPeking University Cancer Hospital and InstituteBeijing 100142China Hua County People's hospital AnyangHenan 456400China Anyang Cancer Hospital AnyangHenan 455000China

Background:The association of lipids and cancer has varied greatly among different cancer types,lipid components and study populations.This study is aimed to investigate the association of serum lipids and the risk of malignant lesions in esophageal squamous epithelium.Methods:In the"Endoscopic Screening for Esophageal cancer in China"(ESECC)trial,serum samples were collected and tested for total cholesterol(TC),triglycerides,low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol at the time of subject enrollment.Cases were defined as malignant esophageal lesions identified by baseline endoscopic examination or by follow-up to May 31,2018.Controls were randomly selected using incidence density sampling in the same cohort.Conditional logistic models were applied to identify the association of serum lipids and the risk of malignant esophageal lesions.Effect modification was evaluated by testing interaction terms of the factor under assessment and these serum lipid indicators.Results:No consistent association between serum lipid levels and esophageal malignant lesions were found in a pooled analysis of 211 cases and 2101 controls.For individuals with a family history of esophageal cancer(EC),high TC,and LDL-C were associated with a significantly increased risk of having malignant lesions(odds ratio[OR]Highvs.Low TC=2.22,95%confidence interval[CI]:1.14-4.35;ORHighvs.Low LDL-C=1.93,95%CI:1.01-3.65).However,a negative association was observed in participants without an EC family history(ORHighvs.Low TC=0.69,95%CI:0.48-0.98,Pinteraction=0.002;ORHighvs.Low LDL-C=0.50,95%CI:0.34-0.76,Pinteractioncancer.The mechanism by which a family history of EC modifies this association warrants further investigation.

关键词： Effect modification Esophageal squamous cell carcinoma Family history Genetic susceptibility Lipids and lipoprotein

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Identification of cancer patients using claims data from health insurance systems: A real-world comparative study

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Chinese Journal of cancer Research 2019年第4期31卷 699-706页

作者： Hongrui Tian Ruiping Xu Fenglei Li Chuanhai Guo Lixin Zhang Zhen Liu Mengfei Liu Yaqi Pan Zhonghu He Yang Ke Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of GeneticsPeking University Cancer Hospital&InstituteBeijing 100142China Anyang Cancer Hospital Anyang 455000China Hua County People’s hospital Anyang 456400China

Objective: To evaluate the accuracy of identifying cancer patients by use of medical claims data in a health insurance system in China, and provide the basis for establishing the claims-based cancer surveillance system in China.Methods: We chose Hua County, Henan Province as the study site, and randomly selected 300 and 1,200 qualified inpatient electronic medical records(EMRs) as well as the New Rural Cooperative Medical Scheme(NCMS) claims records for cancer patients in Hua County People’s hospital(HCPH) and Anyang Cancer Hospital(ACH) in 2017. Diagnostic information for NCMS claims was evaluated on an individual level, and sensitivity and positive predictive value(PPV) were calculated taking the EMRs as the gold standard.Results: The sensitivity of NCMS was 95.2%(93.8%-96.3%) and 92.0%(88.3%-94.8%) in ACH and HCPH,respectively. The PPV of the NCMS was 97.8%(96.7%-98.5%) in ACH and 89.0%(84.9%-92.3%) in HCPH.Overall, the weighted and combined sensitivity and PPV of NCMS in Hua County was 93.1% and 92.1%,respectively. Significantly higher sensitivity and PPV in identifying patients with common cancers than noncommon cancers were detected in HCPH and ACH separately(Pcancer patients by use of the NCMS is accurate on individual level, and it is therefore feasible to conduct claims-based cancer surveillance in areas not covered by cancer registries in China.

关键词： NCMS claims data cancer surveillance sensitivity positive predictive value

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Chinese Journal of cancer Research 2018年第2期30卷 240-253页

作者： Hui Wang Yaqi Pan Chuanhai Guo Fenglei Li Ruiping Xu Mengfei Liu Zhen Liu Fangfang Liu Hong Cai Yang Ke Zhonghu He Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Laboratory of Genetics Peking University Cancer Hospital & Institute Beijing 100142 China Hua County People's hospital Anyang 456400 China Anyang Cancer Hospital Anyang 455000 China

Objective： There have been few population-based studies evaluating health related quality of life（HRQOL） in rural populations in China, and this study aimed to assess the current status of and risk factors for HRQOL in a general rural population in high risk region of esophageal cancer in China.Methods： From November 2015 to September 2016, 12,085 permanent residents aged 45–69 years from 257 villages in the Endoscopic Screening for Esophageal cancer in China（ESECC） trial（Clinical Trials.gov：NCT01688908） randomly selected from Hua County, Henan Province, China were interviewed. The EQ-5 D-3 L,a generic measure of HRQOL, and a questionnaire were used to assess their HRQOL and potential risk factors.Results： Among all the participants, 30.62% of the participants reported problems in at least one EQ-5 D dimension. Pain/discomfort（25.52%） was the most frequently reported problem followed by anxiety/depression（7.97%）, mobility（5.82%）, usual activities（2.61%） and self-care（1%）. These rural residents had a mean EQ-5 D index score of 0.948, and lower EQ-5 D index scores were associated with older age, female gender, lower levels of household annual per capita income, living alone, using shallow wells as main source of drinking water, exposure to family members smoking, testiness, unhealthy dietary habits, overweight or obesity, upper gastrointestinal cancer related symptoms and chronic diseases.Conclusions： Rural residents in China have a relatively low quality of life. Health promotion programs in this population should focus on the elderly, especially elderly women and the elderly living alone. Improving basic living circumstances and primary medical care services should be priorities. Results of this study will also serve as the basis for the cost-utility evaluation in our ESECC screening trial.

关键词： HRQOL EQ-5D rural population China

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Association of genotypes of rs671 within ALDH2 with risk for gastric cardia adenocarcinoma in the Chinese Han population in high-and low-incidence areas

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cancer Biology & Medicine 2017年第1期14卷 60-65页

作者： Lian-Qun Zhang Xin Song Xue-Ke Zhao Jia Huang Peng Zhang Lu-Wen Wang Hui Meng Jian-Wei Ku Guo-Qiang Kong Tao Jiang Xin-Min Li Xiao-Long Lv Teng Ma Guo Yuan Min-Jie Wu Shou-Jia Hu Shuang Lv Tang-Juan Zhang Ling-Fen Ji Zong-Min Fan Neng-Chao Wang Yao-Wen Zhang Fu-You Zhou Li-Dong Wang Henan Key Laboratory for Esophageal cancer Research of the First Affiliated hospital Zhengzhou UniversityZhengzhou 450052China anyang Tumor hospital Anyang 455000China cancer Research Center Xinxiang Medical UniversityXinxiang 453003China

Objective: This study aimed to determine if gastric cardia adenocarcinoma(GCA) risk was associated with the lys(A or *2) allele at the rs671(glu504lys) polymorphism within the aldehyde dehydrogenase 2(ALDH2) gene in a Chinese Han population. We also aimed to investigate ALDH2 genotypic distributions between subjects from high- and low-incidence areas for both GCA and esophageal squamous cell carcinoma(ESCC).Methods: We designed a case-control study including 2,686 patients with GCA and 3,675 control subjects from high- and lowincidence areas for both GCA and ESCC in China. Taq Man allele discrimination assay was used to genotype the rs671 polymorphism. χ~2 test and binary logistic regression analysis were used to estimate the odds ratios for the development of GCA,and multivariate ordinal logistic regression was used to analyze ALDH2 genotypic distributions among different groups.Results: Compared with ALDH2*1/*1 homozygotes, ALDH2*1/*2 and ALDH2*2/*2 carriers did not increase the risk for GCA in the Chinese Han population(P>0.05). Interestingly, the ratio of homozygous or heterozygous ALDH2 *2 carriers in highincidence areas for both GCA and ESCC was lower than that in low-incidence areas(P<0.001).Conclusions: Genotypes of rs671 at ALDH2 may not increase GCA susceptibility in Chinese Han populations. In addition, the ALDH2 genotypic distribution differs between Chinese Han populations from high- and low-incidence areas for both GCA and ESCC. Our findings may shed light on the possible genetic mechanism for the dramatic geographic differences of GCA occurrence in China.

关键词： Gastric cardia adenocarcinoma rs671 ALDH2

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PIWI-interacting RNAs: Mitochondria-based biogenesis and functions in cancer

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Genes & Diseases 2021年第5期8卷 603-622页

作者： Jingfen Su Anthony Concilla Dianzheng Zhang Fang Zhao Fangfang Shen Hao Zhang Fuyou Zhou anyang Key Laboratory for Esophageal cancer Research Anyang Cancer HospitalThe Forth Affiliated Hospital of Henan University of Science and TechnologyAnyangHenan Province455000PR China Department of Bio-Medical Sciences Philadelphia College of Osteopathic MedicinePhiladelphiaPA 19131USA Key Laboratory for Tumor Translational Medicine The Third Affiliated HospitalXinxiang Medical UniversityXinxiangHenan Province453000PR China Institute of Precision cancer Medicine and Pathology Jinan University Medical CollegeGuangzhouGuangdong Province510630PR China

PIWI-interacting RNA(piRNAs),once thought to be mainly functioning in germlines,are now known to play an essential role in somatic and cancerous tissues.Ping-pong cycle initi-ation and mitochondria-based phased production constitute the core of the piRNA biogenesis and these two processes are well conserved in mammals,including humans.By being involved in DNA methylation,histone marker deposition,mRNA degradation,and protein modification,piRNAs also contribute to carcinogenesis partly due to oncogenic stress-induced piRNA dysre-gulation.Also,piRNAs play important roles in cancer stemness,drug resistance,and tumor immunology.Results from liquid biopsy analysis of piRNA can be used in both cancer diagnoses and cancer prognoses.A combination of targeting piRNA with other therapeutic strategies could be groundbreaking cancer treatment.

关键词： Carcinogenesis Clinical utility Mitochondria-based phased production Ping-pong cycle Piwi-interacting RNAs

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Truth telling for patients with esophageal squamous cell carcinoma in Henan,China

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cancer Biology & Medicine 2017年第1期14卷 83-89页

作者： Lian-Qun Zhang Pei-Nan Chen Hai-Ling Wang Li Sun Xue-Ke Zhao Xin Song Min-Jie Wu Tang-Juan Zhang Ling-Fen Ji Wei-Li Han Zong-Min Fan Yuan Yuan Hai-Jun Yang Jian-Po Wang Fu-You Zhou Yi-Jun Qi Li-Dong Wang anyang Tumor hospital Anyang 455000China Henan Key Laboratory for Esophageal cancer Research of The First Affiliated hospital Zhengzhou UniversityZhengzhou 450052China The Second Affiliated hospital of Zhengzhou University Zhengzhou 450014China The Affiliated cancer hospital of Zhengzhou University Zhengzhou 450008China Key Laboratory of Cellular and Molecular Immunology College of MedicineHenan UniversityKaifeng 475004China

Objective: This study aims to investigate the truth-telling status and the relevant factors of esophageal squamous cell carcinoma(ESCC) patients in Henan, China.Methods: A cross-sectional study from April to June 2015 using questionnaires was given to 301 family members of hospitalized ESCC patients based in three affiliated hospitals of Zhengzhou University(i.e., The First hospital, The Second hospital, and Tumor hospital) and anyang Tumor hospital.Results: Among the 41.9%(126/301) hospitalized ESCC patients who knew of their true diagnoses, only 4.0% patients were informed by their corresponding responsible doctors, 39.7% by their family members, and 56.3% by themselves. Univariate analyses showed that disclosure of confirmed ESCC diagnosis to patients was correlated with gender, family history of cancer(FHC), education level, vocation, hospital administrative level, and attitudes of family members(P hospitalized in municipal hospitals exhibited a low rate of truth telling.Conclusions: Truth telling for ESCC patients in Henan is not prevalent and may be improved through consultation with family members, particularly for patients with a negative FHC, poor education, manual occupation, and advanced stages.

关键词：鳞状细胞癌食管癌河南中国肿瘤医院家庭成员控股公司横断面调查

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Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis:A multicenter propensity scorematched cohort study

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Chinese Journal of cancer Research 2020年第6期32卷 794-803页

作者： Ziying Lei Jiahong Wang Zhi Li Baozhong Li Jiali Luo Xuejun Wang Jin Wang MingchenBa Hongsheng Tang Qingjun He Quanxing Liao Xiansheng Yang Tianpei Guan Han Liang Shuzhong Cui Department of Abdominal Surgery Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou 510095China Department of General Surgery Affiliated Tumor Hospital of Zhengzhou UniversityTumor Hospital of Henan ProvinceZhengzhou 450008China Department of Surgery Anyang Tumor HospitalAnyang 455000China Department of Oncology Guangzhou Medical UniversityGuangzhou 510095China Department of Gastrointestinal cancer Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center of CancerKey Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjin 300060China

Objective:Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis(PM)in gastric cancer(GC).Hyperthermic intraperitoneal chemotherapy(HIPEC)combined with complete cytoreductive surgery(CRS)has shown promising outcomes but remains controversial.The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM.Methods:This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone(Cx group)or with HIPEC combined with chemotherapy(HIPEC-Cx group)in four Chinese high-volume gastric medical centers between 2010 and 2017.The primary outcomes were median survival time(MST)and 3-year overall survival(OS).Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias.Results:Of 663 eligible patients,498 were matched.The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months,respectively[hazard ratio(HR)=0.71,95%confidence interval(95%CI),0.58-0.88;P=0.002].The 3-year OS rate was 10.1%(95%CI,5.4%-14.8%)and 18.4%(95%CI,12.3%-24.5%)in the Cx and HIPEC-Cx groups,respectively(P=0.017).The complication rates were comparable.The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone(4.6±2.4 d vs.2.7±1.8 d,P<0.001;14.2±5.8 d vs.11.4±7.7 d,P<0.001),respectively.The median follow-up period was 33.2 months.Conclusions:Compared with standard systemic chemotherapy,HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM,without compromising patient safety.

关键词： Gastric cancer peritoneal metastasis hyperthermic intraperitoneal chemotherapy chemotherapy

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Characterization of 500 Chinese patients with cervical esophageal cancer by clinicopathological and treatment outcomes

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cancer Biology & Medicine 2020年第1期17卷 218-226页

作者： Peinan Chen Xueke Zhao Fuyou Zhou Xin Song Shoujia Hu Yan Jin Xianzeng Wang Xuena Han ZongminFan Ran Wang Bei Li Wenli Han Panpan Wang Jilin Li Lixin Wan Liguo Zhang Qide Bao Fubao Chang Yanru Qin Zhiwei Chang Jianwei Ku Haijun Yang Ling Yuan Jingli Ren Xuemin Li Lidong Wang State Key Laboratory of Esophageal cancer Prevention&Treatment and Henan Key Laboratory for Esophageal cancer Research of The First Affiliated hospital Zhengzhou UniversityZhengzhou 450052China Department of Thoracic Surgery Anyang Tumor HospitalAnyang 455000China Department of Histology and Embryology School of Basic Medical SciencesXinxiang Medical UniversityXinxiang 453000China Department of Thoracic Surgery Linzhou People's HospitalLinzhou 456550China Department of Pathology and Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450000China Department of Pathology Linzhou Esophageal Cancer HospitalLinzhou 456550China Department of Oncology Nanyang Central HospitalNanyang 473000China Department of Thoracic Surgery Xinxiang Central HospitalXinxiang 453000China Department of Oncology Anyang District HospitalAnyang 455000China Department of Thoracic Surgery Linzhou Center HospitalLinzhou 456550China Department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Department of Gastroenterology The Second Affiliated Hospital of Nanyang Medical CollegeNanyang 473000China Department of Pathology Anyang Tumor HospitalAnyang 455000China Department of Radiotherapy The Affiliated Cancer Hospital of Zhengzhou University(Henan Cancer Hospital)Zhengzhou 450000China Department of Pathology The Second Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Department of Pathology Hebei Provincial Cixian People's HospitalCixian 056500China

Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer(CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC patients.Methods: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database(1973–2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments(radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan–Meier method were used to compare the continuous variables and survival.Results: Among the 500 CEC patients, 278(55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients(99.2%) were diagnosed with squamous cell carcinoma. In 171(34.2%) patients who received surgery, 22(12.9%) had undergone laryngectomy. In 322(64.4%) patients who received non-surgical treatments, 245(76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy(P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.

关键词： Cervical esophageal cancer survival esophagectomy radiochemotherapy

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Oral microbiome and risk of malignant esophageal lesions in a high-risk area of China:A nested case-control study

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Chinese Journal of cancer Research 2020年第6期32卷 742-754页

作者： Fangfang Liu Mengfei Liu Ying Liu Chuanhai Guo Yunlai Zhou Fenglei Li Ruiping Xu Zhen Liu Qiuju Deng Xiang Li Chaoting Zhang Yaqi Pan Tao Ning Xiao Dong Zhe Hu Huanyu Bao Hong Cai Isabel Dos Santos Silva Zhonghu He Yang Ke Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of GeneticsPeking University Cancer Hospital&InstituteBeijing 100142China Novogene Co. LtdBeijing 100080China Hua County People's hospital Anyang 456400China Anyang Cancer Hospital Anyang 455000China Department of Non-communicable Disease Epidemiology London School of Hygiene&Tropical MedicineLondon WC1E 7HTUK

Objective:We aimed to prospectively evaluate the association of oral microbiome with malignant esophageal lesions and its predictive potential as a biomarker of risk.Methods:We conducted a case-control study nested within a population-based cohort with up to 8 visits of oral swab collection for each subject over an 11-year period in a high-risk area for esophageal cancer in China.The oral microbiome was evaluated with 16 S ribosomal RNA(rRNA)gene sequencing in 428 pre-diagnostic oral specimens from 84 cases with esophageal lesions of severe squamous dysplasia and above(SDA)and 168 matched healthy controls.DESeq analysis was performed to identify taxa of differential abundance.Differential oral species together with subject characteristics were evaluated for their potential in predicting SDA risk by constructing conditional logistic regression models.Results:A total of 125 taxa including 37 named species showed significantly different abundance between SDA cases and controls(all Pcancer provided an area under the receiver operating characteristic curve(AUC)of 0.89(95%CI,0.84-0.93).Cross-validation and sensitivity analysis,excluding cases diagnosed within 1 year of collection of the baseline specimen and their matched controls,or restriction to screenendoscopic-detected or clinically diagnosed case-control triads,or using only bacterial data measured at the baseline,yielded AUCs>0.84.Conclusions:The oral microbiome may play an etiological and predictive role in esophageal cancer,and it holds promise as a non-invasive early warning biomarker for risk stratification for esophageal cancer screening programs.

关键词： Early warning biomarker esophageal squamous cell carcinoma oral microbiome risk prediction

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An individualized immune signature of pretreatment biopsies predicts pathological complete response to neoadjuvant chemoradiotherapy and outcomes in patients with esophageal squamous cell carcinoma

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Signal Transduction and Targeted Therapy 2020年第1期5卷 886-895页

作者： Chaoqi Zhang Guochao Zhang Nan Sun Zhen Zhang Liyan Xue Zhihui Zhang Haijun Yang Yuejun Luo Xiaoli Zheng Yonglei Zhang Yufen Yuan Ruixue Lei Zhaoyang Yang Bo Zheng Le Wang Yun Che Feng Wang Sihui Wang Shugeng Gao Qi Xue Yi Zhang Jie He Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Biotherapy Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052 HenanChina Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Pathology Anyang Cancer HospitalThe Fourth Affiliated Hospital of Henan University of Science and TechnologyAnyang 455000 HenanChina Department of Radiotherapy The Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450008 HenanChina Department of General Surgery The Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450008 HenanChina Department of Otology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052 HenanChina

No clinically available biomarkers can predict pathological complete response(pCR)for esophageal squamous cell carcinomas(ESCCs)with neoadjuvant chemoradiotherapy(nCRT).Considering that antitumor immunity status is an important determinant for nCRT,we performed an integrative analysis of immune-related gene profiles from pretreatment biopsies and constructed the first individualized immune signature for pCR and outcome prediction of ESCCs through a multicenter analysis.During the discovery phase,14 differentially expressed immune-related genes(DEIGs)with greater than a twofold change between pCRs and less than pCRs(anyang cohorts)with AUCs of 0.890 and 0.859,respectively.Importantly,a multivariate analysis showed that the signature was the only independent predictor for pCR.In addition,patients with high predictive scores showed significantly longer overall and relapse-free survival across multiple centers(P<0.05).This is the first,validated,and clinically applicable individualized immune signature of pCR and outcome prediction for ESCCs with nCRT.Further prospective validation may facilitate the combination of nCRT and immunotherapy.

关键词： esophageal patients immunity

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