Molecular Features Of Early Gastric Cancer And Precancerous Lesions And Endoscopic Treatment Decision-making

Gastric cancer is a common gastrointestinal tumor,and the mortality ranked fourth of cancer related mortality.Early diagnosis is important for a good prognosis,and the quality of life for early gastric cancer(EGC)patients could be improved by endoscopic resection.However,EGCs is asymptomatic and lack of laboratory characteristics.So far,endoscopy is still the common diagnostic method for high risk population of gastric cancer.It is in great need to identify novel biomarker for early gastric cancer to improve the pertinence of endoscopy.And the treatment method of early gastric cancer depends to the depth of invasion.Conventional endoscopy and endoscopic ultrasonography(EUS)are used to estimate the invasion depth of EGCs,but estimates made by either technique are often inaccurate.In order to stratify the risk of gastric cancer in high-risk population,and accurate estimation of the invasion depth of EGCs prior to resection,this dissertation is consisted of three parts:the first one is to study the genome expression profiling in early gastirc cancers and gastric precancerous lesions,the second part is to study plasma microRNAs as diagnostic biomarker for gastric precancerous lesions and early cancers,and the third part is to develop a predictive model for endoscopic treatment of early gastric cancer.Part ? The Genome Expression Profiling in Early Gastirc Cancers and Gastric Precancerous LesionsObjective:By analyzing the miRNA and mRNA expression profile of patients with EGC,HGIN and gastritis,to find the molecular and functional changes in gastric early carcinogenesis.Methods:The mRNA and miRNA expression profiling was performed on 11 gastritis samples,18 HGIN samples and 19 EGC samples with Agilent microarrays.We integrated the information from the molecular levels of miRNA and mRNA,and built the miRNA-mRNA correlation molecular network.To find the related important genes in gastric early carcinogenesis and a GO(gene ontology)enrichment analysis was performed to explore the molecular functional of the important genes.Results:The gene expression patterns of EGC and HGIN tissues were similar,but were significant different with gastritis tissues.The related biological function of the over-expressed genes in EGC and HGIN tissues were mainly focused on the immune response and inflammation response.As for the down-regulated genes,their biological function were in the category of signal transduction,ion transmembrane transport,digestion,eating behavior and locomotory behavior.By integrating the information from the molecular levels of miRNA and mRNA,we built the miRNA-mRNA correlation molecular network and found that the gene expression patterns of EGC was significant different with gastritis tissues.The biological function of the up-regulated genes in EGC were in the category of cancer,immune response and inflammation response.And the related biological function of the down-regulated genes were in the category of signaling pathway and axon guidance.Conclusions:The gene expression changes at the early stage of gastric cancer.Immune response and inflammation response contribute to the malignant progression of gastric neoplasia.Part ? Study on Plasma MicroRNAs as Diagnostic Biomarker for Gastric Precancerous Lesions and Early CancersObjective:To examine the expression of miRNA in plasma of patients with early gastric cancer,gastric precancerous lesions and gastritis and evaluated the feasibility of using plasma miRNAs as non-invasive diagnostic biomarkers for gastric precancerous lesions and early cancers.Methods:Differential miRNAs between EGC and non-cancer population were selected by miRNA microarray data and miRCancer database.The differentially expressed miRNA were validated using quantitative real-time PCR in the plasma of 58 gastritis patients,20 LGIN patients,34 HGIN patients and 38 EGC patients.Developed a diagnostic model by multivariable logistic regression analyses and its discriminative power was assessed by area under the receiver operating characteristic(AUROC)curves analysis.Results:The expression levels of miR-19a-3p was significantly higher in plasma of LGIN,HGIN and EGC patients compared with those of gastritis patients(all P<0.001);the AUROC of miR-19a-3p was 0.770(95%CI 0.694-0.835)for diagnosing LGIN/HGIN/EGC patients.The expression level of miR-483-5p was also significantly higher in plasma of LGIN,HGIN and EGC patients compared with those of gastritis patients;the AUROC of miR-483-5p was 0.758(95%CI 0.681-0.825)for diagnosing gastric precancerous lesions and early cancers.Compared with gastritis and LGIN patients,the level of miR-22-3p in EGC patients was significantly higher(P=0.001 for EGC vs gastritis and P=0.010 for EGC vs LGIN).But there was no different between LGIN patients and gastritis patients for the level of miR-22-3p.A model that incorporated of age,miR-19a-3p and miR-483-5p discriminated between gastritis patients and LGIN/HGIN/EGC patients with an AUROC of 0.840(95%CI 0.771-0.895).A cutoff value of-0.08 identified LGIN/HGIN/EGC patients with 87.7%sensitivity and 62.8%specificity.Conclusions:The expression level of plasma miR-19a-3p and miR-483-5p in LGIN/HGIN/EGC patients were higher than gastritis patients,they could be as a potential non-invasive diagnostic biomarker for gastric precancerous lesions and early cancers.Part III Develop a predictive model for endoscopic treatment of early gastric cancerBackground&Aims:Accurate estimation of the invasion depth prior to resection is crucial for the therapeutic decision-making of early-stage gastric cancers(EGCs).Conventional endoscopy and endoscopic ultrasonography(EUS)are used to estimate the invasion depth of EGCs,but estimates made by either technique are often inaccurate.We developed a model to determine the invasion depth of EGCs using conventional endoscopy and EUS findings,with pathology results as the reference.Methods:We performed a retrospective study of 195 patients diagnosed with gastric cancers who underwent endoscopy and EUS followed by endoscopic submucosal dissection or surgery at the Peking Union Medical College Hospital in China from January 2006 to December 2015.Lesions were classified based on endoscopic features and staged by EUS,and issue specimens were analyzed histologically.Based on pathology analyses,lesions(n=205)were assigned to categories of:mucosa invasion or minute invasion into the submucosal layer less than 500 ?m from the muscularis mucosae(M-SM1)or penetration of 500 ?m or more(?SM2).The lesions were randomly assigned to derivation(138 lesions)and validation sets(67 lesions).Multivariable logistic regression analyses were used to associate endoscopic and EUS features with invasion depth,and a model was developed based on these data;its discriminative power was assessed by area under the receiver operating characteristic(AUROC)curves analysis.Results:Remarkable redness(as a reddish area similar to regenerative epithelium;odds ratio(OR),5.42;95%CI,1.32-22.29),abrupt cutting of converging folds(sudden interruption of converging folds;OR,8.58;95%CI,1.65-44.72),lesions location in the upper third of the stomach(OR,10.26;95%CI,2.19-48.09)and deep invasion based on EUS findings(OR,16.53;95%CI,4.48-61.15)significantly associated with ?SM2.A model that incorporated these 4 variables discriminated between M-SM1 and ?SM2 lesions with an AUROC of 0.865 in the derivation set and 0.797 in the validation set.In the derivation set,a cutoff score of 8 identified lesions as ?SM2 with 54%sensitivity and 97%specificity.The model correctly predicted the invasion depth 89.86%of lesions;it overestimated the depth of 2.17%of lesions.Conclusions:In a retrospective analysis of endoscopy,EUS and pathology data,we developed a model to identify EGCs with invasion depth ?SM2 based on endoscopy and EUS findings.This model might be used to reduce overestimation of gastric tumor depth and prevent unnecessary gastrectomy.Objective To analyze the red blood cell transfusion in the department of gastroenterology of Peking Union Medical College Hospital in 2015 in order to provide some references for rational use of blood in clinical practice.Methods Medical records of patients hospitalized in department of gastroenterology of Peking Union Medical College Hospital who received red blood cell transfusion from January to October in 2014 and 2015 were reviewed.The clinical information including blood transfusion volume,transfusion case number,the cause of transfusion,and the hemoglobin values before transfusion were summarized.Results The red blood transfusion volumes were 403 units in department of gastroenterology in 2015,transfused in 76 person-times,accounted for 8.4%of the total red blood cell transfusion volume in all non-surgical departments.Gastrointestinal bleeding was the disease which consumed the most blood(204U).The average transfusion volume was the highest in lymphoma(21.5U per person).9%of the patients need emergency surgical hemostasis.The median hemoglobin value before red blood cell transfusion of in-patients in the department of gastroenterology was 65.5g/L meeting the recommended threshold of Chinese guidelines on blood transfusion.Conclusions The large volume of blood transfusion in the department of gastroenterology may be due to the type and severity of conditions treated in this department.Strengthening cooperation among departments and optimizing the schedule of surgery may help in reducing the volume of blood transfusion in department of gastroenterology.