Validation of quercetin in the treatment of colon cancer with diabetes via network pharmacology and molecular dynamics simulation
Author:
Wang Mingqing1, Cao Guodong1, Zhou Weiguo1, Cao Wei1, Yang Kang1, Zhang Xun1, Zhang Peng1, Zhang Zehua1, Chen Bo1, Hu Kongwang1, Xiong Maoming1
Affiliation:
1. First Affiliated Hospital of Anhui Medical University
Abstract
Abstract
Objectives
Patients suffering from colon cancer with diabetes (CRC-Diabetes) are more likely to metastasis and relapse when compare with colon cancer (CRC). However, there is a lack of a prognostic model and efficient treatment for CRC-Diabetes. Based on these clinical requirements, this study built a prognosis model for CRC-Diabetes and analyzed whether quercetin could be used for CRC-Diabetes treatment through network pharmacology, Molecular dynamics simulation and bioinformatics .
Methods
Firstly, the differentially expressed genes (DEG) in colon cancer and the related genes in diabetes were screened, and the intersection genes of the two gene clusters were used to construct the prognosis model. Then the potential prognostic markers were screened by univariate Cox proportional hazards regression and lasso regression. Furthermore, multivariate Cox proportional hazards regression was used to construct the prognosis model of CRC-Diabetes. Consequently, quercetin related target genes were screened. The intersection of quercetin target genes with CRC-Diabetes genes was used to find the potential target for quercetin in the treatment of CRC-Diabetes. Molecular docking and molecular dynamics simulation were used to screen reliable targets for quercetin in treatment of CRC-Diabetes.
Results
There are 1008 intersection genes between colon cancer and diabetes. The constructed multivariate Cox proportional hazards regression model based on the above genes shows that the ROC values of 1, 3 and 5 years are 0.787, 0.793 and 0.85 respectively. There are 101 intersection genes in quercetin and CRC-Diabetes. Through molecular docking, seven proteins (HMOX1, ACE, MYC, MMP9, PLAU, MMP3, MMP1) were selected as potential targets of quercetin. We conducted molecular dynamics simulation of quercetin and the above proteins respectively, and found that the binding structure of quercetin with MMP9 and PLAU was relatively stable, which can be considered as a reliable target for quercetin treatment of CRC-Diabetes.
Conclusions
Based on TCGA, TTD, Drugbank and other databases, a prediction model that can effectively predict the prognosis of colon cancer patients with diabetes was constructed. Quercetin can treat colon cancer patients with diabetes by influencing PLAU and its downstream pathways.
Publisher
Research Square Platform LLC
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