食管癌专病队列研究

项目来源

国家重点研发计划(NKRD)

项目主持人

魏文强

项目受资助机构

中国医学科学院肿瘤医院

项目编号

2016YFC0901400

立项年度

2016

立项时间

未公开

研究期限

未知 / 未知

项目级别

国家级

受资助金额

1835.00万元

学科

精准医学研究

学科代码

未公开

基金类别

精准医学研究重点专项

关键词

食管癌 ; 癌前病变 ; 高发区 ; 筛查 ; Esophageal cancer ; Precancerous lesions ; high risk areas ; screening

参与者

陈茹

参与机构

北京市肿瘤防治研究所;汕头大学医学院

项目标书摘要:本课题旨在依据统一的高发现场食管癌及其癌前病变人群队列建立标准规范,建立覆盖人群不少于10万人的前瞻性人群队列。收集人群流行病学基线调查信息、病理诊断信息和治疗随诊信息,采集血液、病变组织等生物样本,建立生物样品库和与之对应的数据信息库,为精准医学重大专项食管癌专病研究共享平台的搭建提供资源。目前,本课题已制定了9个高发区人群队列相关标准规范,出版了《上消化道癌筛查及早诊早治技术方案(2020年试行版)》,编制了《食管癌专病队列数据集》团体标准已正式送审。在8个高发区构建前瞻性队列121503人,收集队列人群的流行病学调查信息,同时收集内镜和病理诊断等诊断信息,并与调查信息进行链接。建成了以林州为中心样本库,磁县、扬中、肥城、盐亭、北肿和汕头为分中心的生物样本库。样本库建筑面积超过1200平方米,配备-80℃超低温冰箱28台,收集血液标本62808例,组织标本39041例,样本信息与流行病学调查信息以唯一编码相链接。在主动随访基础上,依托全国肿瘤登记中心平台,以二代身份证作为个体识别信息,在全国肿瘤登记系统中对队列人群的食管癌发病情况和人群生存情况进行追踪和调查,比对发病和死亡信息,完善随访数据,建立主动随访和被动随访相结合的高效动态随访体系,使随访率达到90%以上。建立食管癌专病队列研究项目数据管理平台,为食管癌防控研究提供了丰富的数据和样本资源。

Application Abstract: This project aims to establish standards for the cohort of esophageal cancer and its precancerous lesions in high-risk areas and establish a prospective cohort that covers a population of no less than 100,000.To collect epidemiological baseline survey information,pathological diagnosis information and treatment follow-up information,and to collect blood and tissue samples to establish a biobank with corresponding database.And to provide resources for the establishment of a shared platform for precision medicine of esophageal cancer research.At present,this project has formulated 9 standards related to esophageal cancer cohort in high-risk areas,published the"Upper Gastrointestinal Cancer Screening and Early Diagnosis and Treatment Technical Program(Trial Version in 2020)",and formulated the group standard of"Esophageal Cancer Special Disease Cohort Data Set"that has been formally submitted for review.This project constructed a prospective cohort of 121,503 subjects from 8 high risk areas,and collected their epidemiological survey information,as well as endoscopic diagnostic information and pathological diagnosis at the same time,and linked with each other.A biological sample bank with Linzhou as the center sample bank and Cixian,Yangzhong,Feicheng,Yanting,Beizhong and Shantou as the sub-centers has been established.The sample library has a building area of over 1,200 square meters,equipped with 28-80℃ ultra-low temperature refrigerators,collecting 62,808 blood samples and 39,041 tissue samples.The sample information and epidemiological survey information are linked with a unique code.On the basis of active follow-up,relying on the platform of the National Cancer Registry,using the second-generation ID card as individual identification information,the incidence death information was compared,and the survival of the cohort populations are tracked and investigated in the national cancer registry to improve the follow-up data,and to establish an efficient and dynamic follow-up system that combines active follow-up and passive follow-up,so that the follow-up rate can reach more than 90%.This project also establish a data management platform for esophageal cancer and provides a wealth of data and sample resources for esophageal cancer prevention and control research.

项目受资助省

北京市

项目实施周期(年)

5

  • 排序方式:
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  • 1.[Status and prospect of esophageal cancer screening].

    • Li, M J;Chen, R;Wang, S M;Wei, W W
    • 《Zhonghua zhong liu za zhi [Chinese journal of oncology]》
    • 2025年
    • 47卷
    • 1期
    • 期刊

    Esophageal cancer is one of the global public health problems, which is a serious threat to life and health. Screening is not only an important main measures to reduce the incidence and mortality of esophageal cancer, but also an effective strategy for early prevention and early treatment. There are significant differences in the screening status of esophageal adenocarcinoma and esophageal squamous cell carcinoma cancer between China and abroad. Internationally, there are several guidelines for screening and monitoring of Barrett's esophagus and esophageal adenocarcinoma, but most guidelines do not recommend screening in the general population. The primary screening by sponge ball then endoscopic diagnosis is a new focus. In China, the screening of esophageal cancer and its precancerous lesions is mainly esophageal squamous cell carcinoma, which has been relatively mature and gradually transformed from population screening to opportunistic screening. However, due to the high cost, high technical difficulty and certain invasiveness, it is difficult to popularize and be applied widely; and the canceration rate of precancerous lesions is low, so it is very important to control the cost of screening and scientific follow-up. Moreover, high-risk population should raise their awareness of cancer prevention, actively take primary prevention and the initiative to participate in screening. About medicine institutions, it is urgent to improve the awareness and capacity of early screening. The multi-disciplinary research cooperation, minimally invasive, simple and economical screening methods and multi-omics biomarkers are still explored to detect and concentrate high-risk populations, which will help to optimize screening programs of esophageal cancer and further reduce the incidence and mortality of esophageal cancer.

    ...
  • 2.Association between CDH1 methylation and esophageal cancer risk: a meta-analysis and bioinformatics study

    • 关键词:
    • CDH1 methylation; esophageal cancer; diagnosis; biomarker;meta-analysis; bioinformatics study;SQUAMOUS-CELL CARCINOMA; E-CADHERIN EXPRESSION; PROMOTERHYPERMETHYLATION; BARRETTS-ESOPHAGUS; PROGRESSION; GENES; INFECTION;ISLAND
    • Fan, Zhiyuan;Chen, Ru;Li, Minjuan;Gu, Jianhua;Li, Xinqing;Wei, Wenqiang
    • 《EXPERT REVIEW OF MOLECULAR DIAGNOSTICS》
    • 2022年
    • 22卷
    • 9期
    • 期刊

    Objective The aim is to evaluate the association of CDH1 methylation with esophageal cancer (EC) risk. Methods The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify relevant articles. Pooled odds ratios (ORs) with 95% confidence interval (CI) were estimated using the fixed- or random-effects models. The pooled sensitivity and specificity were calculated to assess the diagnostic value of CDH1 methylation for EC. The results of the meta-analysis were validated using The Cancer Genome Atlas and Gene Expression Omnibus databases. Results Thirteen studies consisting of 1,633 samples were included. A high CDH1 methylation was significantly associated with an increased risk of EC (OR = 10.40, 95% CI = 6.29-17.18). Furthermore, CDH1 methylation status was related to tumor status, lymph node status, and metastasis. For the diagnosis of EC, the pooled sensitivity and specificity of CDH1 methylation were 0.57 (95% CI = 0.39-0.74) and 0.89 (95% CI = 0.81-0.94), respectively. Bioinformatics analysis showed that CDH1 methylation occurred more frequently in EC tissues than in normal controls, in good agreement with the results of the meta-analysis. Conclusion A significant association was found between CDH1 methylation and EC risk. We therefore suggest that CDH1 methylation can serve as a promising diagnostic marker for EC.

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  • 3.Novel DNA methylation markers for early detection of gastric cardia adenocarcinoma and esophageal squamous cell carcinoma

    • 关键词:
    • gastric cardia adenocarcinoma; esophageal squamous cell carcinoma;high-grade dysplasia; DNA methylation markers; early detection;ESOPHAGOGASTRIC JUNCTION; CANCER; PSCA; GENES
    • Fan, Zhiyuan;Hao, Jiajie;He, Feifan;Jiang, Hao;Wang, Jinwu;Li, Minjuan;Li, Xinqing;Chen, Ru;Wei, Wenqiang
    • 《SCIENCE CHINA-LIFE SCIENCES》
    • 2024年
    • 期刊

    Gastric cardia adenocarcinoma (GCA) and esophageal squamous cell carcinoma (ESCC) present significant health challenges in China, often diagnosed at advanced stages with poor prognoses. However, effective biomarkers for early detection remain elusive. This study aimed to integrate methylome and transcriptome data to identify DNA methylation markers for the early detection of GCA and ESCC. In the discovery stage, we conducted Infinium MethylationEPIC array analysis on 36 paired GCA and non-tumor adjacent tissues (NAT), identifying differentially methylated CpG sites (DMCs) between GCA/ESCC and NAT through combined analyses of in-house and publicly available data. In the validation stage, targeted pyrosequencing and quantitative real-time RT-PCR were performed on paired tumor and NAT samples from 50 GCA and 50 ESCC patients. In the application stage, an independent set of 438 samples, including GCA, ESCC, high- and low-grade dysplasia (HGD/LGD), and normal controls, was tested for selected DMCs using pyrosequencing. Our analysis validated three GCA-specific, two ESCC-specific, and one tumor-shared DMCs, exhibiting significant hypermethylation and decreased expression of target genes in tumor samples compared with NAT. Leveraging these DMCs, we developed a GCA-specific 4-marker panel (cg27284428, cg11798358, cg07880787, and cg00585116) with an area under the receiver operating characteristic curve (AUC) of 0.917, effectively distinguishing between cardia HGD/GCA patients and cardia LGD/normal controls. Similarly, an ESCC-specific 3-marker panel (cg14633892, cg04415798, and cg00585116) achieved an AUC of 0.865 in distinguishing esophageal HGD/ESCC cases. Furthermore, integrating cg00585116, age, and alcohol consumption yielded a tumor-shared logistic model with good discrimination for two cancer/HGD (AUC, 0.767; 95% confidence interval, 0.720-0.813). The mean AUC of the model after 5-fold cross-validation was 0.764. In summary, our study identifies novel DNA methylation markers capable of accurately distinguishing GCA/ESCC and HGD from LGD and normal controls. These findings offer promising prospects for targeted DNA methylation assays in future minimally invasive cancer screening methods.

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  • 4.Somatic CDKN2A copy number variations are associated with the prognosis of esophageal squamous cell dysplasia

    • 关键词:
    • CDKN2A; Somatic copy number variations; Esophageal squamous cellcarcinoma; Esophageal neoplasms; Squamous intraepithelial lesions; DNAcopy number variations; Prognosis; Prospective study;MALIGNANT-TRANSFORMATION; PROMOTER METHYLATION; FOLLOW-UP; CANCER;PROGRESSION; CARCINOMA; AMPLIFICATION; IMPACT; CHINA; RISK
    • Fan, Zhiyuan;Zhou, Jing;Tian, Yuan;Qin, Yu;Liu, Zhaojun;Gu, Liankun;Dawsey, Sanford;Wei, Wenqiang;Deng, Dajun
    • 《CHINESE MEDICAL JOURNAL》
    • 2024年
    • 137卷
    • 8期
    • 期刊

    Background: Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. Methods: This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. Results: A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower (P = 0.008), while the cumulative progression rate was higher (P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys (P = 0.004) in the multivariable analysis. Conclusion: The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

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  • 5.Mobilizing China and the Global Community to Confront the Treatment Desert for Pediatric Solid Tumors

    • 关键词:
    • CHILDREN
    • Wang, Shuhang;Jiang, Yale;Zheng, Rongshou;Yu, Yue;Wei, Wenqiang;Li, Ning
    • 《CANCER DISCOVERY》
    • 2024年
    • 14卷
    • 1期
    • 期刊

    Pediatric solid tumors are distinct clinical entities that impose heavy socioeconomic burden and while their incidence has increased in recent years, treatment options are often limited, with only 27 drugs approved for pediatric solid tumors in the United States, and fewer still, 13, in China. The scale of the unmet medical need is immense and new efforts are urgently needed to develop efficient therapeutics and improve these children's lives.

    ...
  • 6.Gastric Mucosal Status and Risk of Gastric Cancer in High-Risk Individuals: A Population-Based, Multicenter Prospective Study in China.

    • 关键词:
    • gastric cancer; gastric mucosal status; incidence; prospective study
    • Liu, Han;Song, Song;Geng, Xianyi;Chen, Ru;Zheng, Rongshou;Wei, Wenqiang;Li, Ni;Chen, Wanqing;Ren, Jiansong
    • 《Cancer medicine》
    • 2024年
    • 13卷
    • 19期
    • 期刊

    OBJECTIVE: This study explored the distributions of gastric mucosal status and their links to gastric cancer within urban high-risk individuals in China.; METHODS: From 2014 to 2015, a questionnaire survey was administered among individuals aged 40 to 69years, residing for over 3years in seven selected cities across China. Utilizing the questionnaire data, high-risk individuals for gastric cancer were screened. These identified high-risk individuals were invited to undergo endoscopy, followed by pathological examinations conducted for those with suspicious lesions. Prior cancer patients and those newly diagnosed with gastric cancer were excluded, and the remaining endoscopic participants were prospectively followed up until December 2021.; RESULTS: The prospective study followed 8911 individuals at high risk of gastric cancer for a median duration of 6.77years. The incidence density of gastric cancer was 58.55 per 100,000 person-years. At baseline, the distributions of subjects across normal gastric mucosa, gastritis/ulcer/polyp, atrophic gastritis/intestinal metaplasia, and intraepithelial neoplasia groups were 47.09%, 36.27%, 9.57%, and 7.07%, respectively. Compared with normal gastric mucosa, the hazard ratios (HRs) for gastric cancer in the other groups were 0.89 [95% confidence interval (95%CI): 0.38-2.08], 1.52 (95%CI: 0.50-4.66), and 4.63 (95%CI: 1.98-10.82). When using the 40-54 age group as the reference, the HR for 55-69 age group was 3.49 (95%CI: 1.52-7.98).; CONCLUSION: Among high-risk individuals with gastric cancer, the proportions of individuals exhibiting different gastric mucosal status inversely correlated with the severity of mucosal lesions, whereas the risk of gastric cancer progressively escalated with the increasing severity of mucosal lesions and advancing age. © 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

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  • 7.Non-invasive early detection on esophageal squamous cell carcinoma and precancerous lesions by microbial biomarkers combining epidemiological factors in China.

    • 关键词:
    • Early detection; Esophageal cancer; Metagenomic sequencing; Microbiota; Precancerous lesions
    • Li, Minjuan;Shao, Dantong;Fan, Zhiyuan;Qin, Junjie;Xu, Junming;Huang, Qingru;Li, Xinqing;Hua, Zhaolai;Li, Jun;Hao, Changqing;Wei, Wenqiang;Abnet, Christian C
    • 《Journal of gastroenterology》
    • 2024年
    • 期刊

    BACKGROUND: Microbiota may be associated with esophageal squamous cell carcinoma (ESCC) development. However, it is not known the predictive value of microbial biomarkers combining epidemiological factors for the early detection of ESCC and precancerous lesions.; METHODS: A total of 449 specimens (esophageal swabs and saliva) were collected from 349 participants with different esophageal statuses in China to explore and validate ESCC-associated microbial biomarkers from genes level to species level by 16S rRNA sequencing, metagenomic sequencing and real-time quantitative polymerase chain reaction.; RESULTS: A bacterial biomarker panel including Actinomyces graevenitzii (A.g_1, A.g_2, A.g_3, A.g_4), Fusobacteria nucleatum (F.n_1, F.n_2, F.n_3), Haemophilus haemolyticus (H.h_1), Porphyromonas gingivalis (P.g_1, P.g_2, P.g_3) and Streptococcus australis (S.a_1) was explored by metagenomic sequencing to early detect the participants in Need group (low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and ESCC) vs participants without these lesions as the Noneed group. Significant quantitative differences existed for each microbial target in which the detection efficiency rate was higher in saliva than esophageal swab. In saliva, the area under the curve (AUC) based on the microbial biomarkers (A.g_4P.g_3H.h_1S.a_1F.n_2) was 0.722 (95% CI 0.621-0.823) in the exploration cohort. Combining epidemiological factors (age, smoking, drinking, intake of high-temperature food and toothache), the AUC improved to 0.869 (95% CI 0.802-0.937) in the exploration cohort, which was validated with AUC of 0.757 (95% CI 0.663-0.852) in the validation cohort.; CONCLUSIONS: It is feasible to combine microbial biomarkers in saliva and epidemiological factors to early detect ESCC and precancerous lesions in China. © 2024. Japanese Society of Gastroenterology.

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  • 8.Early Contrast-Enhanced MR for Diagnosing Complete Tumor Response of Locally Advanced Esophageal Squamous Cell Carcinoma After Neoadjuvant Therapy: A Retrospective Comparative Study.

    • 关键词:
    • Esophageal squamous cell carcinoma; Magnetic resonance imaging; Neoadjuvant therapy
    • Shi, Yan-Jie;Yan, Shuo;Yang, Xin;Guan, Zhen;Li, Xiao-Ting;Wang, Lin-Lin;Dai, Liang;Sun, Ying-Shi
    • 《Annals of surgical oncology》
    • 2024年
    • 期刊

    BACKGROUND: This study assessed the performance of early contrast-enhanced magnetic resonance (ECE-MR) in the detecting of complete tumor response (ypT0) in patients with esophageal squamous cell carcinoma following neoadjuvant therapy.; PATIENTS AND METHODS: Preoperative MR images of consecutive patients who underwent neoadjuvant therapy and surgical resection were reviewed retrospectively. The accuracy of ECE-MR and T2WI+DWI was evaluated by comparing the findings with pathological results. Receiver operating characteristic curve analysis was used to assess the diagnostic performance, and DeLong method was applied to compare the areas under the curves (AUC). Chi-squared analysis was conducted to explore the difference in pathological changes.; RESULTS: A total of 198 patients (mean age 62.6±7.8 years, 166 men) with 201 lesions were included. The AUC of ECE-MR was 0.85 (95% CI 0.79-0.90) for diagnosing ypT1-4, which was significantly higher than that of T2WI+DWI (AUC 0.69, 95% CI 0.63-0.76, p<0.001). The diagnostic performance of both T2WI+DWI and ECE-MR improved with increasing tumor stage. The AUCs of ECE-MRI were higher in ypT1 and ypT2 tumors than T2WI+DWI. Degree 2-3 tumor-infiltrating lymphocytes and neutrophils were commonly seen in ypT0 tumors misdiagnosed by ECE-MR.; CONCLUSIONS: Visual evaluation of ECE-MR is a promising diagnostic protocol for the detection of complete tumor response, especially for differentiation with early stage tumors. The accurate diagnosis of complete tumor response after neoadjuvant therapy using imaging modalities is of important significance for clinical decision-making for patients with esophageal squamous cell carcinoma. It is hoped that early contrast-enhanced MR will provide supportive advice for the development of individualized treatment options for patients. © 2024. Society of Surgical Oncology.

    ...
  • 9.Suboptimal dietary quality is associated with mental symptoms among adults aged 40 years and over in China: A population-based cross-sectional study

    • 关键词:
    • Dietary quality; Anxiety; Depression; Chinese diet balance index-16;VEGETABLE CONSUMPTION; DEPRESSIVE SYMPTOMS; OLDER TAIWANESE; NUTRIENTINTAKE; GLYCEMIC INDEX; WEIGHT-GAIN; RISK; ANXIETY; HEALTH; PATTERNS
    • Ma, Shanrui;Zhu, Juan;Xie, Shuanghua;Chen, Ru;Li, Xinqing;Wei, Wenqiang
    • 《JOURNAL OF AFFECTIVE DISORDERS》
    • 2023年
    • 340卷
    • 期刊

    Background: The previous studies an association between dietary patterns and psychiatric symptoms. However, few studies have examined the association of quality of dietary patterns and anxiety, depressive symptoms in the Chinese population. Methods: Between 2017 and 2019, a population-based, cross-sectional survey was carried out in China. Uniformed questionnaires collected the demographic characteristics and food data. The dietary quality of the adults was evaluated using the revised Diet Balance Index 2016 (DBI-16). We measured anxiety and depression symptoms using the the Generalized Anxiety Disorder (GAD)-7 and Patient Health Questionnaire (PHQ)-9. Results: A total of 73,737 participants were recruited during the survey period. 17.6 % and 13.7 % of residents suffer from anxiety and depression symptoms, respectively. The DBI-16 indicates that participants with anxiety or depression symptoms had higher scores of low bound score (LBS, refers to inadequate food intake) and dietary quality distance (DQD, refers to unbalanced food intake) than those without anxiety or depression. The logistic regression models showed that high levels of LBS and DQD problems were more strongly associated with anxiety (LBS:OR = 1.20, DQD:OR = 1.30) and depressive symptoms (LBS:OR = 1.21, DQD:OR = 1.44). On the contrary, higher bound score (HBS, refers to excessive food intake) was significantly negatively correlated with symptoms of anxiety and depression. Moreover, each increase in the food group was associated with 4 % lower odds of anxiety and 6 % lower odds of depression symptoms. Limitations: Cross-sectional design and self-reporting of psychological symptoms and dietary information limit the generalizability of the results. Conclusion: The dietary quality of adults aged 40 years and over in China is suboptimal, with excessive and inadequate food intake simultaneously. Dietary imbalance, and low dietary diversity may be related to anxiety and depressive symptoms.

    ...
  • 10.[Application of novel non-endoscopic device in the screening and early diagnosis of esophageal cancer].

    • 关键词:
    • Biomarker; Early diagnosis; Esophageal neoplasms; Novel non-endoscopic device; Screening
    • Fan, Z Y;Chen, R;Wei, W W
    • 《Zhonghua zhong liu za zhi [Chinese journal of oncology]》
    • 2023年
    • 45卷
    • 8期
    • 期刊

    Esophageal cancer (EC) is a dreadful disease with a poor prognosis and poses heavy health burden worldwide. Developing effective methods to identify high-risk individuals is urgently needed for preliminary screening before endoscopy. The novel non-endoscopic device has the potential advantages of low cost, simple operation, and minimal invasiveness. Approximately 90% of participants can swallow the device successfully with high safety profiles, and sufficient esophageal exfoliated cells can be collected for cytological examination and biomarker detection. Cytological examination based on the device combined with trefoil factor 3 (TFF3) protein or DNA methylation examinations could effectively screen Barrett's esophagus-associated dysplasia and early esophageal adenocarcinoma, but large prospective studies are needed to further validate the diagnostic value of this device to improve the quality of evidence. Although the device-based cytological examination in combination with biomarker detection holds promise in the early screening of esophageal squamous dysplasia and early esophageal squamous cell carcinoma, related research is still in its infancy, and there is still a lack of sufficient evidence for population screening in China. Active research into the application of this novel non-endoscopic device in EC screening and early diagnosis is of great significance for optimizing EC screening strategies and improving the early diagnosis of EC.

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