| Objectives: The purpose of this study was to analyze the value of screening indicators for Early Gastric Cancer screening through the implementation of Early Gastric Cancer screening in Gansu Province,and to evaluate and optimize screening strategies.At the same time,to select novel miRNA biomarkers for predictive diagnosis of Early Gastric Cancer.Our research is divided into two parts:1 This study depends on the design and implement of “Early Cancer Screening Program of Upper Gastrointestinal Tract of Gansu Province”,including hospitals from50 counties and cities in Gansu Province as project sites to establish “Internet Plus Digestive System Tumor Early Diagnosis and Treatment of MDT Wisdom Medical Platform”and a biological sample bank.After analyzing the “Upper Gastrointestinal Health Factor Questionnaire” obtained from the initial screening,the screening strategy for Early Gastric Cancer(EGC)was validated and optimized.2 Using the biological sample library resources of the project,the differential expression profiles of plasma and plasma Exosomes(EXO)miRNAs in Early Gastric Cancer(EGC),Advanced Gastric Cancer(AGC)and benign gastritis(BG)were detected by miRNAs chip,and some miRNAs with predictive diagnostic value for Early Gastric Cancer were screened.A novel miRNAs marker predictive diagnostic model of receiver operating characteristic curves was validated and refined in subsequent screening programs.Methods:1 Combine the recommendations of epidemiologists and local hospitals to select the city and county hospitals with radiation and demonstration functions to establish the “Early Cancer Screening Program of Upper Gastrointestinal Tract of Gansu Province” project site,and establish “Internet plus digestive system tumor early diagnosis and treatment of MDT wisdom medical platform”.Inviting domestic and foreign famous digestive endoscopy experts to go to the project site to carry out academic lectures,"hands-on" standardized operation training,convene endoscopy combined pathology multidisciplinary academic conference,improve the project site hospital digestive system tumor early diagnosis and treatment theory and practice level;follow the “Upper Gastrointestinal Health Factor Questionnaire” combined with Helicobacter pylori(Hp)and other auxiliary examinations to screen high-risk groups-endoscopic findings of Gastric Cancer positive cases-Gastric Cancer patients undergoing individualized clinical treatment,establish a follow-up cohort for patients with precancerous diseases-improve the implementation process of the biologicalsample bank,actively carry out screening programs and improve the level of diagnosis and treatment of upper gastrointestinal tract cancer in the project site hospital;The results of the “Upper Gastrointestinal Health Factors Questionnaire”were analyzed,and the risk factors associated with Early Gastric Cancer were analyzed and the screening strategy was improved.2 Using the biobank established by the project to study the expression profiles of plasma and plasma Exosomes miRNA microarrays in patients with Early Gastric Cancer,Advanced Gastric Cancer and benign gastritis,and with the help of bioinformatics analysis to screen out several target miRNAs that are unique to Early Gastric Cancer and may be differentiated from Advanced Gastric Cancer and benign gastritis.Validating miRNAs with good predictive diagnosis for Early Gastric Cancer in plasma and plasma Exosomes through the reverse transcription quantitative real-time polymerase chain reaction(qRT-PCR),and to construct a miRNA marker prediction diagnosis model with selected several miRNAs for predictive diagnosis of Early Gastric Cancer.Results:1 “Early Cancer Screening Program of Upper Gastrointestinal Tract of Gansu Province” was established in Feb 2016 and officially launched in Longnan City,Gansu Province in July.As of Jan 2019,“the Early Cancer Screening Program of the Upper Gastrointestinal Tract of Gansu Province” has successfully established 50 project sites in 86 counties and cities in Gansu Province.18 members of the “Internet plus digestive system tumor early diagnosis and treatment of MDT wisdom medical platform”,covering a population of 14.913 million people,and conducting 23 early cancer screening projects.There were 45 academic reports,more than 500 training staff,3119 cases of endoscopic examination,2707 cases of “Upper Gastrointestinal Health Factor Questionnaire”,and 121 cases of upper gastrointestinal cancer the detection rate of early cancer reached 67.77%.Through the statistical analysis of the“Upper Gastrointestinal Health Factor Questionnaire”,it was found that the high-risk factors listed in the “Consensus of Early Gastric Cancer Screening and Endoscopic Diagnosis and Treatment in China”(2014,Changsha)have limited value in Early Gastric Cancer screening and need further improvement.And it was confirmed that the new Gastric Cancer screening and scoring system established by “Expert Consensus of Early Gastric Cancer Screening Process in China(Draft)”(2017,Shanghai)can better target high-risk groups from natural populations.Using this as a screening strategy to screen out high-risk groups for endoscopic intensive examination,combined with the training of the standardization of digestive endoscopy combined with pathological diagnosis in the primary hospital of the project site,the detection rate of Early Gastric Cancer can be significantly improved.2 Expression profiles of plasma and plasma Exosomes miRNA microarray in patients with Early Gastric Cancer,Advanced Gastric Cancer and benign gastritis has been investigted.It was found that there were 117 differential expressions in the plasma miRNAs microarray expression profile,and 191 of the plasma exosome miRNAs microarray expression profiles were differentially expressed.And 14 differentially expressed miRNAs in plasma were verified by RT-qPCR,then combined detection of circulating plasma miR-1180-3p,miR-425-5p,miR-122-5p,miR-24-3p and miR-4632-5p was established.Abnormal expression of miRNAs can be used as a predictive marker for the diagnosis of Early Gastric Cancer.Conclusions:1 The implementation of the “Early Cancer Screening Program of Upper Gastrointestinal Tract of Gansu Province” confirms that the high-risk factors of Gastric Cancer are included in the population through the “Upper Gastrointestinal Health Factor Questionnaire”,combined with age,gender and serum Hp antibody,Pepsinogen(PGR)and gastrin 17(G-17)detection of a new Gastric Cancer screening scoring system for Gastric Cancer risk grading,endoscopic screening techniques such as white light endoscopy,electronic staining plus magnification and esophageal iodine staining were used as the main tools for endoscopic screening in high risk population,combined with the functions of "Internet plus digestive system tumor early diagnosis and treatment of MDT wisdom medical platform",which can significantly improve detection rate of Early Gastric Cancer,lay the foundation for early detection and early treatment of Early Gastric Cancer.2 Abnormal expression of circulating plasma miRNAs(miR-1180-3p,miR-425-5p,miR-122-5p,miR-24-3p,miR-4632-5p)can be used as a new specific organism for predicting Early Gastric Cancer.Biomarkers can be combined with endoscopy to improve the detection rate of Early Gastric Cancer.It is proposed to validate and apply this model in a larger population of screening programs to establish a predictive diagnosis of Early Gastric Cancer with high sensitivity and specificity liquid biopsy technology. |
