Humoral And Endoscopic Diagnosis Of Early Gastric Cancer And Precancerous Lesions

PART ONE.The application of circular RNA for early gastric cancer diagnosisBackground:Circular RNAs(circRNAs)are essentially expressed in cells and are dysregulated in cancers.They can be detected in exosomes,plasma,gastric fluid and urine.They are ideal biomarkers because they are more stable and detectable than linear RNAs.Aims:This study aims to explore the feasibility of plasma circRNAs as biomarkers for diagnosis of early gastric cancer(EGC)and high-grade intraepithelial neoplasia(HGIN).Methods:The expression profiles of tissue circRNAs in four patients with EGC and four patients with chronic gastritis(CG)were analyzed by RNA sequencing.The relative expression of targeting circRNAs were quantified by real-time quantitative polymerase chain reaction in tissue and plasma of 17 patients with EGC,16 patients with HGIN and 59 patients with CG.The relative expression of targeting circRNAs were further quantified by real-time quantitative polymerase chain reaction in plasma of 10 patients with EGC,10 patients with HGIN and 40 patients with CG for validation.The relative expression of targeting circRNAs among patients with EGC,HGIN and CG were compared by univariable analysis.The area under the curve for the diagnosis of EGC and HGIN by tissue and plasma circRNAs were performed.Results:A total of 20986 circRNAs were detected in tissue RNA sequencing and four circRNAs,namely circCDCP1,circKANSL1L,circRPRD1A,and circTRIM33,were selected as targeting circRNAs.The expression of tissue circRPRD1A was significantly higher in EGC and HGIN tissues than CG tissues.Plasma circRPRD1A had a specificity of 88.0%-91.7%and a sensitivity of 40.0%-83.3%for the diagnosis of HGIN,with the area under the curve of 0.617-0.913.The expression of tissue circCDCP1 in HGIN was significantly higher than CG,while the expression of plasma circCDCP1 was downregulated in patients with EGC.The area under the curve for the diagnosis of EGC by plasma circCDCP1 was 0.538-0.671,with a sensitivity of 30.0%-41.2%and a specificity of 92.5%-94.1%.Conclusion:The expression of circRNAs was different in EGC tissues from CG tissues.The expression of circRNAs in HGIN tissued began to change compared to CG tissues.Plasma circCDCP1 and circRPRD1A are potential biomarkers for diagnosis of EGC and HGIN.PART TWO.The value of magnifying endoscopy-narrow band image in identifying early gastric cancer and predicting clinical outcomes of precancerous gastric lesionsBackground:Early diagnosis and treatment of gastric cancer are efficient ways to improve disease survival.Low-grade intraepithelial neoplasia(LGIN)is a precursor of gastric cancer and can progress to malignancy.However,endoscopic forceps biopsy(EFB)obtains a little piece of tissue and can’t always provide sufficient information for diagnosis.LGIN diagnosed by EFB can have cancerous composition already.Therefore,the management of LGIN remains to be discussed.Aims:To evaluate the value of magnifying endoscopy-narrow band image(ME-NBI)and plasma circRNAs in identifying early gastric cancer and predicting clinical outcomes of precancerous gastric lesions.Methods:The clinical records of patients diagnosed as LGIN by EFB from 2007 to 2017 were retrospectively reviewed.Patients evaluated by both white light endoscopy(WLE)and ME-NBI initially,and with lesions resected for final diagnosis or were followed up for more than one year were enrolled.Two endoscopists blindly reviewed both WLE images and ME-NBI images of lesions separately,identified lesion features of the index endoscopy and made their endoscopic diagnosis based on the index endoscopy.Univariate and multivariate analysis were performed to compare features of lesions with different clinical outcomes.Kaplan-Meier analysis was made to analyze factors related to disease progression.Area under the curves and the Cohen’ s kappa coefficient were respectively calculated to compare diagnosis efficacy of WLE and ME-NBI and consistency between endoscopists.The expression of plasma circRNAs were relatively quantified by qRT-PCR,and compared among patients with different short-term outcomes.Results:Overall,121 patients with 125 lesions were enrolled.Lesions finally diagnosed as malignancies were more seen as singular,with non-flat gross types,nodular or ulcerative surfaces,clear and irregular margins,diameters larger than 1 cm by WLE;with irregular microvascular patterns,absent or irregular microsurface pattern,white obscure substances,clear demarcation line and meet the "vessels plus surface" criterion by ME-NBI.Flat gross types,diameters larger than 1 cm and meet the "vessels plus surface" criterion were independent factors for malignancies with the OR as 0.046(95%CI 0.007-0.282,P=0.001),4.342(95%CI 1.188-15.869,P=0.026)and 15.829(95%CI 3.749-66.821,P<0.001),respectively.The area under the curves for recognition of malignancies were 0.787-0.794 by WLE,and 0.831-0.850 by ME-NBI.The kappa coefficients between two endoscopists were 0.530 by WLE and 0.668 by ME-NBI.The relative expression level of plasma circRNAs among patients with different short-term clinical outcomes were not significantly different.Conclusion:The diagnostic efficacy and consistency between endoscopists for recognizing malignancies initially diagnosed as LGIN using EFB were better by ME-NBI than by WLE,especially for identifying lesions progressed to malignancies in short-time and lesions regressed to benignancy after long-time following up.The value of plasma circRNAs for identifying patients with different short-term clinical outcomes was limited.