Identification of Significant Modules and Targets of Xian-Lian-Jie-Du Decoction Based on the Analysis of Transcriptomics, Proteomics and Single-Cell Transcriptomics in Colorectal Tumor

Abstract

Purpose Colorectal cancer (CRC) remains the third most common tumor worldwide. Ulcerative colitis (UC) could cause chronic inflammation and ulcers in the colon and rectum. UC is a risk factor for a high incidence of CRC, and the incidence of UC-associated CRC (UC-CRC) is still increasing. Chinese medicine prescription, Xian-Lian-Jie-Du decoction (XLJDD), has been proven its efficacy in some UC-CRC patients. However, the mechanism of XLJDD in treating UC-CRC remains unknown. This study aimed to investigate the mechanism of XLJDD in treating UC-CRC. Methods We constructed an AOM/DSS mouse model that could simulate the various stages of UC-CRC in humans. XLJDD and its 5 main components are used to treat the AOM/DSS model, respectively. With the power of high-throughput sequencing technology, we described the mechanism of XLJDD from transcriptomics, proteomics, and single-cell transcriptomics. Results Our results showed that XLJDD could effectively suppress the occurrence and development of colorectal tumors. Using the weighted correlation network analysis (WGCNA), several mRNA and protein modules that respond to XLJDD have been identified. Moreover, two essential genes, Mfsd2a and Ccdc85c, were caught our attention. They were prognostic markers in CRC patients, and their expression could be significantly modulated by XLJDD, showing their potential as effective targets of XLJDD. In addition, we also discovered that XLJDD could affect the cell composition of the colorectal tumor environment, especially in the infiltration of B cells. Conclusion We demonstrated that XLJDD could prevent the initiation and development of colorectal tumors by modulating the expression of Mfsd2a and Ccdc85c and reducing the infiltration of B cells in the tumor microenvironment of colorectal tumor.

A Combination of Microarray-Based Profiling and Biocomputational Analysis Identified miR331-3p and hsa-let-7d-5p as Potential Biomarkers of Ulcerative Colitis Progression to Colorectal Cancer

“…Therefore, a lower expression of CCDC85C was a predictor of poorer survival in CRC patients [37]. Many studies confirmed differential expression of circRNAs between normal colon and CRC cell lines [38,39]. Analysis of a ceRNA sub-network showed that circRNA-SHPRH and circ-CEP128 regulated the expression of hsa-miR-331-3p and hsa-miR-145-5p, respectively.…”

Branched-Chain Amino Acid Degradation Pathway was Inactivated in Colorectal Cancer: Results from a Proteomics Study

“…In this study, membrane proteomic analysis was conducted on the intestinal mucosa from an AOM/DSS-induced mouse model of colon cancer. Although previous proteomic studies utilizing the AOM/DSS mouse model have explored proteins related to colon cancer [32][33][34][35][36][37], membrane proteomic studies are limited, hindering the investigation of lower abundance and insoluble membrane proteins. In this study, membrane proteomic analysis revealed the regulation of metabolic pathways in tumor tissues compared with that in the adjacent normal colon tissues.…”

Efficacy and safety of Xian-Lian-Jie-Du optimization decoction as an adjuvant treatment for prevention of recurrence in patients with stage IIIB/IIIC colon cancer: study protocol for a multicentre, randomized controlled trial

“…XLJDOD is an empirical prescription used as an adjuvant treatment of colorectal cancer for more than 10 years in China. Basic biological research confirms that XLJDOD effectively inhibits tumor cell proliferation and migration, modulates tumor microenvironment, regulates the function of immune cells [ 54 – 56 ].…”