Cancer-related genetic variants of Helicobacter pylori strains determined using gastric wash-based whole-genome analysis with single-molecule real-time technology.
Yoshiyuki WatanabeRitsuko OikawaYasuhiro KodakaYoshinori SatoShoko OnoTakeshi KenmochiHideo SuzukiSeiji FutagamiMototsugu KatoHiroyuki YamamotoFumio ItohPublished in: International journal of cancer (2020)
Helicobacter pylori (H. pylori) are a primary factor in the pathogenesis of gastric cancer (GC); GC ranks third among cancer-related mortality. A clear understanding of the H. pylori genome factors underlying GC is necessary to develop more effective methods to prevent GC. A single-molecule real-time DNA sequencing-based H. pylori genome-wide association study analysis was performed using the H. pylori genome present in five early-stage GC (EGC) and five non-GC clinical DNA samples recovered from gastric washes. A total of 275 genes with 702 nucleotide variants (NVs) were found to be common to three or more patients with EGC but no non-GC patients (single-NV: 654/702, 93.2%; multi-NV: 40/702, 5.7%; deletion: 3/702, 0.4%; insertion: 3/702, 0.7%). Gene ontology analysis of H. pylori revealed that genes involved in the mitochondrial electron transport system, glycolytic processes and the TCA cycle were highly enriched. Cancer-related NVs were most frequently found in a member of the Helicobacter outer membrane protein family, hopL. In particular, one of the NVs in hopL was a novel six-nucleotide insertion (1159095̂1159096, TACTTC); this mutant was detected more frequently in a validation set of 50 additional EGC samples (22/50, 44.0%) than in 18 non-GC samples (3/18, 16.7%, P = .04). These results suggest that the hopL variant is associated with the development of GC and may serve as a genetic biomarker of H. pylori virulence and GC risk. Our assay can serve as a potent tool to expand our understanding of bacteria-associated tumorigenesis.
Keyphrases
- single molecule
- helicobacter pylori
- gas chromatography
- early stage
- helicobacter pylori infection
- escherichia coli
- end stage renal disease
- living cells
- genome wide association study
- chronic kidney disease
- dna methylation
- mass spectrometry
- copy number
- high resolution
- pseudomonas aeruginosa
- cardiovascular disease
- circulating tumor
- risk factors
- gene expression
- rectal cancer
- radiation therapy
- circulating tumor cells
- high throughput
- prognostic factors
- simultaneous determination
- solid phase extraction
- tandem mass spectrometry
- patient reported
- anti inflammatory
- solar cells
- bioinformatics analysis
- genome wide identification