A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

[Serological assessment of Helicobacter pylori-specific antibodies and their association with gastric lesions in a high-risk population].

OBJECTIVE: To determine the distributions of six Helicobacter pylori (Hp)-specific antibodies in a high-risk population of gastric cancer (GC) and explore the relationship between Hp virulence factors and precancerous gastric lesions. METHODS: Based on the two intervention trials conducted in Linqu County, the seropositivities for CagA, VacA, GroEL, UreA, HcpC and GGT were assessed by recombinant immunoassay (recomLine) in 623 participants with H. pylori infection determined by (13)C-urea breath test ((13)C-UBT) and/or enzyme linked immunosorbent assay (ELISA). RESULTS: In a total of 623 participants were detected by recomLine analysis, of which 594 were Hp-positive. The seropositivities rates of CagA, VacA, GroEL, UreA, HcpC and GGT were 84.0%, 38.2%, 66.7%, 17.7%, 58.8% and 42.8%, respectively. A total of 523 participants were determined as type I infection of Hp, accounting for 88.1%. Compared with superficial gastritis (SG), the infection rate of Hp type I was higher in the chronic atrophic gastritis (CAG) (P = 0.001). CONCLUSIONS: The results of this population-based study suggest that the virulence factors of Hp may be related to the development of GC in a Chinese high-risk population. The recomLine analysis may serve as a tool for identification of Hp strains and prediction of high-risk population of GC.

[First report on assessment of the status of engraftment after allogeneic hematopoietic stem cell transplantation by using denaturing high-performance liquid chromatography].

Monitoring engraftment of donor cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is supposed to be important for the early diagnosis of graft failure or relapse of malignancy. Several techniques have been reported for this purpose. PCR-based assays analyzing polymorphic short tandem repeats (STR) as markers are attractive because they are sensitive and can be performed rapidly. The intent of this study was to test a novel approach for assessment of donor engraftment using denaturing high-performance liquid chromatography (DHPLC) combined with STR-PCR. The feasibility of this assay and the accuracy of semi-quantitative results were tested in-vitro by using serial DNA mixtures from unrelated individuals. The results showed that dilution experiments of the mock chimerism sample revealed a clear correlation between the percentage of donor or recipient DNA and the proportion of allele peak areas, with the limit of detection for a minor DNA percentage being 5%. Discrimination between donor and recipient was possible in all patients analyzed (n = 51) except for 5 patients whose pre-transplant samples were not available and identical twins in one case. STR results were the same as values obtained by capillary electrophoresis combined with fluorescence labeling multiply PCR. Results were also compared with data obtained with FISH analysis in a subgroup of patients receiving grafts from sex-mismatched donors or with PCR-detectable disease-specific gene products analysis. The results of the microsatellite analysis correlated well with the corresponding clinical findings. Full donor chimerism (FDC) were detected in all patients; decreasing values of donor chimerism were detected concomitantly with the appearance of relapse of disease in 3 patients. Samples from eight patients receiving HLA mismatched-haploidentical transplants from related donors together with cord blood transplants from unrelated donors were analyzed by this method. The results showed all 8 patients achieved FDC derived from related donors. It is concluded that this novel approach allows a rapid, sensitive, economical, auto-mated and non-isotopic STR-PCR testing, thus provides a reliable alternative for assessment of the status of engraftment after allo-HSCT.