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phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer

Chinese Journal of Cancer Research 2019年第5期31卷 771-784页

作者： Han-Chen Huang Xian-Zi Wen Hua Xue Run-Sheng Chen Jia-Fu Ji Lei Xu Key Laboratory of RNA Biology Institute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142China Guangdong Geneway Decoding Bio-Tech Co.Ltd Foshan 528316China Centre for Cognitive Machines and Computational Health(CMaCH) School of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Department of Computer Science and Engineering The Chinese University of Hong KongHong Kong 999077China

Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer(GC)challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. phosphoglucose isomerase, also known as glucose-6-phosphate isomerase(GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state(E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition(EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets.Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients.Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage Ⅱ/Ⅲ. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells.Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis,allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.

关键词： Gastric cancer gene expression profile prognostic biomarker phosphoglucose isomerase tumor metabolism

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phosphoglucose Isomerase Deficiency in <i>Escherichia coli</i>K-12 Is Associated with Increased Spontaneous Mutation Rate

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Advances in Microbiology 2018年第5期8卷 390-405页

作者： Elitsa Boteva Yordan Handzhiyski Maria Kotseva Kirill A. Datsenko Barry L. Wanner Monika Pischetsrieder Roumyana Mironova Institute of Molecular Biology Roumen Tsanev Bulgarian Academy of Sciences Sofia Bulgaria Purdue University West Lafayette USA Harvard Medical School Boston USA Friedrich Alexander University Erlangen-Nuremberg Erlangen Germany

phosphoglucose isomerase (PGI) is a key enzyme in early glycolysis, which catalyzes the reversible isomerization of glucose 6-phosphate (G6Ph) to fructose 6-phosphate. We have constructed an Escherichia coli K12 strain with a deleted pgi gene (Δpgi) and shown that this strain in comparison with the parental strain 1) accumulates higher amount of G6Ph, 2) grows slowly, and 3) exhibits higher spontaneous mutation frequency to rifampicin resistance (Rifr), when grown on high glucose minimal medium. Intriguingly, the spontaneous mutation rate to Rifr was inversely related to the degree of E. coli chromosomal DNA modification with sugar derivatives. We measured higher concentrations of Amadori products, fluorophores (360 nm excitation/440 nm emission) and carboxymethyl residues in the chromosomal DNA of the E. coli parental strain than in DNA of the isogenic Δpgi strain. To explain this apparent paradox we hypothesized that PGI might be implicated in repair of G6Ph-derived lesions in DNA. In favor of our hypothesis, we further demonstrate that protein extract from the E. coli PGI proficient strain but not from the PGI deficient strain catalyzes the release of G6Ph from G6Ph-modified single stranded DNA oligonucleotide and from its hybrid duplex with a complementary peptide nucleic acid.

关键词： phosphoglucose Isomerase Glucose 6-Phosphate E. coli Mutations DNA Repair

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