Summary: | 碩士 === 國立中正大學 === 化學工程研究所 === 106 === According to the statistics of the Ministry of Health and Welfare, the number of patients with colorectal cancer and the number of deaths in Taiwan each year show a rapid increase. Many patients do not have obvious symptoms until they develop bleeding or persistent constipation for a while before they realize the possibility of colorectal cancer. However, it usually takes 5 to 10 years to develop from colorectal polyps to colorectal cancer. Once miss the period of treatment in these years, the cure rate will reduce greatly.
We can reconstruct a tissue-specific metabolic model to study not only the impact on the overall network when subjected to gene regulation but also identify the oncogenes that may cause colon cells to become cancerous. We introduce an algorithm called Cost Optimization Reaction Dependency Assessment (CORDA) to build a tissue-specific manner in this study. Based on the global network model of human metabolism (Recon 2.2 Model) and the data of expression for all protein-coding genes from the human protein atlas (HPA) website, we can reconstruct the genome-scale metabolic model of colon.
Then, according to the Mediterranean diet provided by the Virtual Metabolic Human (VMH) website as the standard for ingesting conditions, Mutant Flux balance analysis (MFBA) was used to simulate the metabolic reprogramming, that occurs in colorectal cancer. In this study, we successfully calculated nine of genes, which causes the distribution of metabolic flux in colon cells to become cancerous. The key oncogene that causes this kind of metabolic reprogramming can also provide researchers further direction and develop specific target drugs or new biomarker in the future.
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