Dataset Information

Glucose metabolism gene polymorphisms and clinical outcome in pancreatic cancer.

ABSTRACT: Altered glucose metabolism is the most common metabolic hallmark of malignancies. The authors tested the hypothesis that glucose metabolism gene variations affect clinical outcome in pancreatic cancer.The authors retrospectively genotyped 26 single nucleotide polymorphisms from 5 glucose metabolism genes in 154 patients with localized disease and validated the findings in 552 patients with different stages of pancreatic adenocarcinoma. Association between genotypes and overall survival (OS) was evaluated using multivariate Cox proportional hazard regression models with adjustment for clinical predictors.Glucokinase (GCK) IVS1 + 9652C > T and hexokinase 2 (HK2) N692N homozygous variants were significantly associated with reduced OS in the training set of 154 patients (P < .001). These associations were confirmed in the validation set of 552 patients and in the combined dataset of all 706 patients (P ? .001). In addition, HK2 R844K variant K allele was associated with a better survival in the validation set and the combined dataset (P ? .001). When data were further analyzed by disease stage, glutamine-fructose-6-phosphate transaminase (GFPT1) IVS14-3094T>C, HK2 N692N and R844K in patients with localized disease and GCK IVS1 + 9652C>T in patients with advanced disease were significant independent predictors for OS (P ? .001). Haplotype CGG of GPI and GCTATGG of HK2 were associated with better OS, respectively, with P values of .004 and .007.The authors demonstrated that glucose metabolism gene polymorphisms affect clinical outcome in pancreatic cancer. These observations support a role of abnormal glucose metabolism in pancreatic carcinogenesis.

SUBMITTER: Dong X

PROVIDER: S-EPMC3961843 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Glucose metabolism gene polymorphisms and clinical outcome in pancreatic cancer.

Dong Xiaoqun X Tang Hongwei H Hess Kenneth R KR Abbruzzese James L JL Li Donghui D

Cancer 20100915 3

<h4>Background</h4>Altered glucose metabolism is the most common metabolic hallmark of malignancies. The authors tested the hypothesis that glucose metabolism gene variations affect clinical outcome in pancreatic cancer.<h4>Methods</h4>The authors retrospectively genotyped 26 single nucleotide polymorphisms from 5 glucose metabolism genes in 154 patients with localized disease and validated the findings in 552 patients with different stages of pancreatic adenocarcinoma. Association between genot ...[more]

PMID: 20845477

Similar Datasets

Project description:Background: Pancreatic cancer is an aggressive tumor with a low 5-year survival rate and primary resistance to most therapy. Amino acid (AA) metabolism is highly correlated with tumor growth, crucial to the aggressive biological behavior of pancreatic cancer; nevertheless, the comprehensive predictive significance of genes that regulate AA metabolism in pancreatic cancer remains unknown. Methods: The mRNA expression data downloaded from The Cancer Genome Atlas (TCGA) were derived as the training cohort, and the GSE57495 cohort from Gene Expression Omnibus (GEO) database was applied as the validation cohort. Random survival forest (RSF) and the least absolute shrinkage and selection operator (LASSO) regression analysis were employed to screen genes and construct an AA metabolism-related risk signature (AMRS). Kaplan-Meier analysis and receiver operating characteristic (ROC) curve were performed to assess the prognostic value of AMRS. We performed genomic alteration analysis and explored the difference in tumor microenvironment (TME) landscape associated with KRAS and TP53 mutation in both high- and low-AMRS groups. Subsequently, the relationships between AMRS and immunotherapy and chemotherapy sensitivity were evaluated. Results: A 17-gene AA metabolism-related risk model in the TCGA cohort was constructed according to RSF and LASSO. After stratifying patients into high- and low-AMRS groups based on the optimal cut-off value, we found that high-AMRS patients had worse overall survival (OS) in the training cohort (a median OS: 13.1 months vs. 50.1 months, p < 0.0001) and validation cohort (a median OS: 16.2 vs. 30.5 months, p = 1e-04). Genetic mutation analysis revealed that KRAS and TP53 were significantly more mutated in high-AMRS group, and patients with KRAS and TP53 alterations had significantly higher risk scores than those without. Based on the analysis of TME, low-AMRS group displayed significantly higher immune score and more enrichment of T Cell CD8+ cells. In addition, high-AMRS-group exhibited higher TMB and significantly lower tumor immune dysfunction and exclusion (TIDE) score and T Cells dysfunction score, which suggested a higher sensitive to immunotherapy. Moreover, high-AMRS group was also more sensitive to paclitaxel, cisplatin, and docetaxel. Conclusion: Overall, we constructed an AA-metabolism prognostic model, which provided a powerful prognostic predictor for the clinical treatment of pancreatic cancer.

Dataset Information

Glucose metabolism gene polymorphisms and clinical outcome in pancreatic cancer.

Publications

Glucose metabolism gene polymorphisms and clinical outcome in pancreatic cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets