Transcriptomic and Metabolomic Profiling in Helicobacter pylori–Induced Gastric Cancer Identified Prognosis- and Immunotherapy-Relevant Gene Signatures

Abstract

Background: Chronic Helicobacter pylori (HP) infection is considered the major cause of non-cardia gastric cancer (GC). However, how HP infection influences the metabolism and further regulates the progression of GC remains unknown.Methods: We comprehensively evaluated the metabolic pattern of HP-positive (HP+) GC samples using transcriptomic data and correlated these patterns with tumor microenvironment (TME)–infiltrating characteristics. The metabolic score was constructed to quantify metabolic patterns of individual tumors using principal component analysis (PCA) algorithms. The expression alterations of key metabolism-related genes (MRGs) and downstream metabolites were validated by PCR and untargeted metabolomics analysis.Results: Two distinct metabolic patterns and differential metabolic scores were identified in HP+ GC, which had various biological pathways in common and were associated with clinical outcomes. TME-infiltrating profiles under both patterns were highly consistent with the immunophenotype. Furthermore, the analysis indicated that a low metabolic score was correlated with an increased EMT subtype, immunosuppression status, and worse survival. Importantly, we identified that the expression of five MRGs, GSS, GMPPA, OGDH, SGPP2, and PIK3CA, was remarkably correlated with HP infection, patient survival, and therapy response. Furthermore, the carbohydrate metabolism and citric acid may be downstream regulators of the function of metabolic genes in HP-induced GC.Conclusion: Our findings suggest that there is cross talk between metabolism and immune promotion during HP infection. MRG-specific transcriptional alterations may serve as predictive biomarkers of survival outcomes and potential targets for treatment of patients with HP-induced GC.

Driver Gene Alterations in Malignant Progression of Gastric Cancer

“…The six GC-related driver genes are also associated with the outcome and treatment response of immunotherapy. PIK3CA indicated an increasing risk of death in gastric cancer patients ( 22 ). B2M shapes the immune landscape of lung adenocarcinoma and causes resistance to PD-1-based immunotherapy ( 23 ).…”

Dickkopf-related protein 1/cytoskeleton-associated protein 4 signaling activation by Helicobacter pylori-induced activator protein-1 promotes gastric tumorigenesis via the PI3K/AKT/mTOR pathway

“…The gene expression profiles obtained by independent research groups using RNA-seq were inconsistent due to the use of diverse cell lines, GC tissues, H. pylori strains, and whole-genome expression arrays[ 31 - 33 ]. The upregulated expression of JUN and FOLS1 was noted in H. pylori NCTC11639-infected AGS cells, but not experimentally verified[ 34 ].…”

Structural Insights into the Roles of PARP4 and NAD+in the Human Vault Cage

“…Hits with the "organelle organization" designation also included KPNB1, which, along with IPO7, regulates nucleocytoplasmic shuttling [44], a previously hypothesized function for vault. Finally, GMPPA, which mediates protein glycosylation as a regulatory subunit in the GDP-mannose biosynthetic enzyme complex, has been linked to tumor growth [45] and chemotherapeutic drug resistance [46], pathologies previously linked to MVP upregulation [4].…”