A systematic review of metabolomic profiling of gastric cancer and esophageal cancer

Objective:Upper gastrointestinal(UGI)cancers,predominantly gastric cancer(GC)and esophageal cancer(EC),are malignant tumor types with high morbidity and mortality rates.Accumulating studies have focused on metabolomic profiling of UGI cancers in recent years.In this systematic review,we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with GC and EC.Methods:A systematic search of three databases(Embase,PubMed,and Web of Science)for molecular epidemiologic studies on the metabolomic profiles of GC and EC was conducted.The Newcastle–Ottawa Scale(NOS)was used to assess the quality of the included articles.Results:A total of 52 original studies were included for review.A number of metabolites were differentially distributed between GC and EC cases and non-cases,including those involved in glycolysis,anaerobic respiration,tricarboxylic acid cycle,and protein and lipid metabolism.Lactic acid,glucose,citrate,and fumaric acid were among the most frequently reported metabolites of cellular respiration while glutamine,glutamate,and valine were among the most commonly reported amino acids.The lipid metabolites identified previously included saturated and unsaturated free fatty acids,aldehydes,and ketones.However,the key findings across studies to date have been inconsistent,potentially due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group.Conclusions:Studies on metabolomics have thus far provided insights into etiological factors and biomarkers for UGI cancers,supporting the potential of applying metabolomic profiling in cancer prevention and management efforts.

Helicobacter pylori antibody responses in association with eradication outcome and recurrence： a population-based intervention trial with 7.3-year follow-up in China

Objective： To identify serum biomarkers that may predict the short or long term outcomes of anti-Helicobacter gylori （H. pylori） treatment, a follow-up study was performed based on an intervention trial in Linqu County, China. Methods： A total of 529 subjects were selected randomly from 1,803 participants to evaluate total anti-H, pylori immunoglobulin G （IgG） and 10 specific antibody levels before and after treatment at 1-, 2- and 7.3-year. The outcomes of anti-H, pylori treatment were also parallelly assessed by 13C-urea breath test at 45-d after treatment and 7.3-year at the end of follow-up. Results： We found the medians of anti-H, pylori IgG titers were consistently below cut-off value through 7.3 years in eradicated group, however, the medians declined in recurrence group to 1.2 at 1-year after treatment and slightly increased to 2.0 at 7.3-year. While the medians were significantly higher （〉3.0 at 2- and 7.3-year） among subjects who failed the eradication or received placebo. For specific antibody responses, baseline seropositivities of FliD and HpaA were reversely associated with eradication failure [for FIiD, odds ratio （OR）=0.44, 95% confidence interval （95% CI）： 0.27-0.73; for HpaA, OR=0.32, 95% Ch 0.I7-0.60]. The subjects with multiple positive specific antibodies at baseline were more likely to be successfully eradicated in a linear fashion （Ptrend=0.006）. Conclusions： Our study suggested that total anti-H, pylori IgG level may serve as a potential monitor of long- term impact on anti-H, pylori treatment, and priority for H. pylori treatment may be endowed to the subjects with multiple seropositive antibodies at baseline, especially for FliD and HapA.

Effects of Helicobacter pylori eradication on the profiles of blood metabolites and their associations with the progression of gastric lesions: a prospective follow-up study

Objective:This study aimed at examining the alterations in metabolomic profiles caused by treatment of H.pylori infection,and the associations between key plasma metabolites and the risk of gastric lesion progression during follow-up after treatment.Methods:An intervention trial was performed in 183 participants,117 of whom were H.pylori positive participants receiving treatment for H.pylori infection.H.pylori positive participants were prospectively followed for 182 to 1,289 days.Untargeted metabolomics assays were conducted on plasma samples collected at baseline,6 months after treatment,and during continued follow-up.Results:We identified 59 metabolites with differential posttreatment changes between participants with successful and failed H.pylori eradication,17 metabolites significantly distinguished participants with successful vs.failed eradication.Two metabolites[PC(18:1(11Z)/14:1(9Z))and(2S)-6-amino-2-formamidohexanamide]showed posttreatment changes positively associated with successful H.pylori eradication,and were inversely associated with the risk of gastric lesion progression among participants with successful eradication.In contrast,9-decenoic acid showed posttreatment changes inversely associated with successful eradication:its level was positively associated with the risk of gastric lesion progression among participants with successful eradication.Although the identified metabolites showed a temporary but significant decline after treatment,the trend generally reversed during continued follow-up,and pretreatment levels were restored.Conclusions:Treatment of H.pylori infection significantly altered plasma metabolic profiles in the short term,and key metabolites were capable of distinguishing participants with successful vs.failed eradication,but might not substantially affect metabolic regulation in the long term.Several plasma metabolites were differentially associated with the risk of gastric lesion progression among participants with successful or failed eradication.

Screening for gastric cancer in China:Advances,challenges and visions

Gastric cancer(GC)is one of the major cancers in China and all over the world.Most GCs are diagnosed at an advanced stage with unfavorable prognosis.Along with some other countries,China has developed the government-funded national screening programs for GC and other major cancers.GC screening has been shown to effectively decrease the incidence of and mortality from GC in countries adopting nationwide screening programs(Japan and Korea)and in studies based on selected Chinese populations.The screening of GC relies mostly on gastroendoscopy,the accuracy,reliability and safety of which have been indicated by previous studies.However,considering its invasive screening approach,requirements on skilled endoscopists and pathologists,and a high cost,developing noninvasive methods to amend endoscopic screening would be highly needed.Numerous studies have examined biomarkers for GC screening and the combination of biomarkers involving pepsinogen,gastrin,and Helicobacter pylori antibodies has been proposed for risk stratification,seeking to narrow down the high-risk populations for further endoscopy.Despite all the achievements of endoscopic screening,evidence on appropriate screening age,intervals for repeated screening,novel biomarkers promoting precision prevention,and health economics need to be accumulated to inform policymakers on endoscopic screening in China.With the guide of Health China 2030 Planning Outline,we have golden opportunities to promote prevention and control of GC.In this review,we summarize the characteristics of screening programs in China and other East Asian countries and introduce the past and current approaches and strategies for GC screening,aiming for featuring the latest advances and key challenges,and illustrating future visions of GC screening.

Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Objective:The accurate prediction of tumor response to neoadjuvant chemoradiotherapy(nCRT)remains challenging.Few studies have investigated pathologic complete response(ypCR)prediction in patients with residual flat mucosal lesions after treatment.This study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer(LARC).Methods:Data of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer Hospital.Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed,and a nomogram was constructed by incorporating the significant predictors.Results:Of the 246 patients with residual flat mucosal lesions included in the final analysis,56(22.8%)had ypCR.Univariate and multivariate analyses showed that pretreatment cT stage(pre-cT)≤T2(P=0.016),magnetic resonance tumor regression grade(MR-TRG)1-3(P=0.001)and residual mucosal lesion depth=0 mm(P<0.001)were associated with a higher rate of ypCR.A nomogram was developed with a concordance index(C-index)of0.759 and the calibration curve showed that the nomogram model had good predictive consistency.The follow-up time ranged from 3.0 to 113.3 months,with a median follow-up time of 63.77 months.The multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival(DFS)or overall survival(OS).Conclusions:Completely flat mucosa,early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after nCRT.Endoscopic mucosal re-evaluation before surgery is important,as it may contribute to decision-making and facilitate nonoperative management or organ preservation.