Bioinformatics Analysis to Screen Key Targets of Curcumin against Colorectal Cancer and the Correlation with Tumor-Infiltrating Immune Cells

Xinyue Han,Yimin Xu,Chao Yang,Xiaoling Fu,Xiaoqiang Liu,Xiangxue Meng,Zhihong Cheng,Cui Guo,Runnan Xie,Qing Ji

doi:10.1155/2021/9132608

Abstract

Purpose Curcumin is a potential drug for the treatment of colorectal cancer (CRC). Its mechanism of action has not been elucidated. This study aims to investigate the mechanism of action of curcumin in the treatment of CRC via bioinformatics methods such as network pharmacology and molecular docking. Methods The targets of curcumin and CRC were obtained from the public databases. The component-targets network of curcumin in the treatment of CRC was constructed by Cytoscape v3.7.2. Through protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), important targets and signaling pathways related to CRC treatment were identified. Finally, the results were verified by molecular docking, and the correlation between the key targets and tumor-infiltrating immune cells (TICs) was analyzed. Results A total of 30 potential targets of curcumin for CRC treatment were collected. The GO function enrichment analysis showed 140 items, and the KEGG pathway enrichment analysis showed 61 signaling pathways related to the regulation of protein kinase activity, negative regulation of apoptosis process, cancer signaling pathway, and PI3K-Akt signaling pathway. The molecular docking results showed that curcumin could be combined with AKT1, EGFR, and STAT3 more stably, and AKT1 has the strongest binding to curcumin. Bioinformatics analysis discovered that the expression of core targets AKT1, EGFR, and STAT3 in CRC was related to TICs. Conclusion This study explored the targets and pathways of curcumin in the treatment of CRC. The core targets are AKT1, EGFR, and STAT3. The study indicated that curcumin has preventive and treatment effects on CRC through multitarget and multipathway, which laid the foundation for follow-up research.

Highlights

Colorectal cancer (CRC) is a complex heterogeneous disease involving multiple genes and epigenetic factors [1]
Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Enrichment Analysis. e GO and KEGG enrichment analysis were performed via DAVID platform. e GO enrichment analysis is composed of biological process (BP), cellular component (CC), and molecular function (MF)
Six targets (AKT1, RAF1, BRAF, epidermal growth factor receptor (EGFR), IKBKB, and STAT3) in the first 20 pathways participated in a high frequency (≥9 times), indicating that they played important roles in CRC

Summary

Introduction

Colorectal cancer (CRC) is a complex heterogeneous disease involving multiple genes and epigenetic factors [1]. According to [2], 147950 new CRC cases resulted in 53200 deaths in the United States. E incidence of CRC is the top three in all tumors, and mortality is the second, which seriously endangers human health [3, 4]. Surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy are the mainstream treatments for CRC. Long-term use of these therapies leads to serious side effects, including nausea and vomiting, oral ulcer, diarrhea, bone marrow suppression, and immunosuppression. Drug resistance commonly occurs in CRC [5, 6]. For patients with advanced CRC, there is no effective treatment [7]

Methods

Results

Conclusion