1. Development of a KRAS-Associated Metabolic Risk Model for Prognostic Prediction in Pancreatic Cancer.
- Author
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Ma Z, Li Z, Ma Z, Zhou Z, Zhuang H, Liu C, Huang B, Zou Y, Zheng Z, Yang L, Gong Y, Huang S, Zhou Q, Zhang C, and Hou B
- Subjects
- Cell Line, Tumor, Deoxycytidine analogs & derivatives, Deoxycytidine pharmacology, Deoxycytidine therapeutic use, Drug Resistance, Neoplasm drug effects, Gene Expression Profiling, Gene Expression Regulation, Neoplastic drug effects, Humans, Mutation genetics, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Phenotype, Prognosis, Proto-Oncogene Proteins p21(ras) genetics, ROC Curve, Reproducibility of Results, Risk Factors, Survival Analysis, Gemcitabine, Models, Biological, Pancreatic Neoplasms metabolism, Proto-Oncogene Proteins p21(ras) metabolism
- Abstract
Background: KRAS was reported to affect some metabolic genes and promote metabolic reprogramming in solid tumors. However, there was no comprehensive analysis to explore KRAS-associated metabolic signature or risk model for pancreatic cancer (PC)., Methods: In the current study, multiple bioinformatics analyses were used to identify differentially expressed metabolic genes based on KRAS mutation status in PC. Then, we developed and validated a prognostic risk model based on the selected KRAS-associated metabolic genes. Besides, we explored the association between the risk model and the metabolic characteristics as well as gemcitabine-associated chemoresistance in PC., Results: 6 KRAS-associated metabolic genes (i.e., CYP2S1, GPX3, FTCD, ENPP2, UGT1A10, and XDH) were selected and enrolled to establish a prognostic risk model. The prognostic model had a high C-index of 0.733 for overall survival (OS) in TCGA pancreatic cancer database. The area under the curve (AUC) values of 1- and 3-year survival were both greater than 0.70. Then, the risk model was validated in two GEO datasets and also presented a satisfactory discrimination and calibration performance. Further, we found that the expression of some KRAS-driven glycolysis-associated genes (PKM, GLUT1, HK2, and LDHA) and gemcitabine-associated chemoresistance genes (i.e., CDA and RMM2) was significantly upregulated in high-risk PC patients evaluated by the risk model., Conclusions: We constructed a risk model based on 6 KRAS-associated metabolic genes, which predicted patients' survival with high accuracy and reflected tumor metabolic characteristics and gemcitabine-associated chemoresistance in PC., Competing Interests: The authors declared that they have no potential competing interests., (Copyright © 2021 Zuyi Ma et al.)
- Published
- 2021
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