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

Author(s):  
Duanrui Liu ◽  
Jingyu Zhu ◽  
Xiaoli Ma ◽  
Lulu Zhang ◽  
Yufei Wu ◽  
...  

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.

2021 ◽  
Author(s):  
Ye Wang ◽  
kaitian Zheng ◽  
Jiancheng Wang ◽  
congjun Wang ◽  
Junqiang Chen

Abstract Background Helicobacter pylori (HP) infection is one of the leading causes of gastric cancer (GC). However, the interaction between HP and the TME, and its carcinogenic mechanism remains unknown. Methods We screened 28 HP-related prognostic genes based on HP infection-related gene markers and HP infection sample datasets (GSE6143 and GSE60662). We then constructed an HPscore system by using the principal component analysis algorithm and successfully quantified the HP modification characteristics of a single GC sample. In addition, we comprehensively analysed the relationship between the HPscore and the clinical characteristics of patients with GC, the immune cell infiltration characteristics of the TME and stemness. Results We successfully identified 28 HP-related prognostic genes that accurately classified the GC population. There are significant differences in survival between different subgroups(high-, low-risk and cluster_1,2). Thereafter, we constructed the HPscore system to systematically evaluate the modification characteristics of the 28 HP-related prognostic genes, and the internal and external validation of the HPscore system suggested similar results: the overall survival rate in the high -HPscore group was poor, and immunological surveillance was reduced, whereas the low-HPscore group had a survival advantage, and was related to the inflammatory response. HPscore was also strongly correlated with the tumour stage, TME cell infiltration and stemness. Conclusions HP-modified characteristics play a crucial role in the TME and tumourigenesis. HPscore evaluation of a single tumour sample can help identify the TME characteristics and the carcinogenic mechanism of GC patients infected with HP, based on which personalised treatment can be administered.


2001 ◽  
Vol 120 (5) ◽  
pp. A82-A82 ◽  
Author(s):  
S MAEDA ◽  
Y MITSUNO ◽  
Y HIRATA ◽  
M AKANUMA ◽  
H YOSHIDA ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A658-A658
Author(s):  
E UMEGAKI ◽  
M TANAKA ◽  
N TAKEUCHI ◽  
K NISHIMURA ◽  
M NANRI ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A657-A657
Author(s):  
A BEDOYA ◽  
J GARAY ◽  
F SANZON ◽  
J BRAVO ◽  
H CORREA ◽  
...  

2007 ◽  
Vol 69 (1) ◽  
pp. 8-10
Author(s):  
Ritsuko KANO ◽  
Yusuke YOSHIZAWA ◽  
Seiji KAWANA ◽  
Taku TSUKUI

2020 ◽  
Vol 04 (04) ◽  
Author(s):  
Shuai Ruan ◽  
Wenjie Huang ◽  
Fang Wen ◽  
Xiaona Lu ◽  
Su Ping Gu ◽  
...  

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