Molecular targets and mechanism analysis of colorectal cancer progression based on multi-dimensional data analysis
10.3760/cma.j.cn115396-20241223-00400
- VernacularTitle:基于多维数据分析的结直肠癌疾病进展分子靶点与机制解析
- Author:
Wentao FU
1
;
Tianzhen ZHANG
;
Xiaobao YANG
;
Hanzheng ZHAO
;
Zhongtao ZHANG
Author Information
1. 首都医科大学附属北京友谊医院普通外科中心 消化健康全国重点实验室 国家消化系统疾病临床医学研究中心，北京 100050
- Keywords:
Colorectal neoplasms;
Single-cell analysis;
Extracellular matrix
- From:
International Journal of Surgery
2025;52(3):150-155
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To unveil the dynamic molecular characteristics of colorectal cancer (CRC) progression, identify key molecules and signaling pathways driving disease development, and provide a theoretical basis for precision diagnosis and treatment.Methods:Differentially expressed genes (DEGs) were identified using DESeq2 based on the TCGA-CRC dataset (556 colorectal cancer samples) and three independent validation cohorts from the GEO database (GSE39582, GSE68468, GSE41258). Mfuzz time-series analysiswas applied to identify gene clusters with continuously upregulated expression during tumor progression. Functional enrichment analysis was performed using clusterProfiler, and protein-protein interaction (PPI) networks were constructed via the STRING online platform to pinpoint hub genes. Single-cell sequencing data (GSE132465/GSE144735) were integrated to resolve the cellular origins and intercellular communication of key genes. The prognostic value of genes was assessed using a univariate Cox proportional hazards model (likelihood ratio test), and single-cell sequencing data were analyzed using the Seurat pipeline with Wilcoxon rank-sum test to identify DEGs.Results:Time-series analysis identified Gene Cluster 4 (containing 186 genes) with a sustained upregulation trend across CRC stages from Ⅰ to Ⅳ. Functional enrichment revealed these genes were significantly involved in extracellular matrix (ECM) remodeling and pathways such as PI3K-Akt and MAPK signaling. PPI network analysis screened 10 hub genes ( COL10A1, THBS2, SPP1, etc.), whose high expression correlated significantly with poor patient prognosis. Single-cell sequencing demonstrated that these hub genes were predominantly expressed in fibroblast subpopulations, while SPP1 was enriched in macrophages. Cell-cell communication analysis confirmed that THBS2-CD47 and SPP1-CD44 were the primary pathways mediating fibroblast-immune/endothelial cell interactions. Conclusion:ECM-related genes are closely associated with the progression of CRC, in which the key molecules THBS2 and SPP1 may drive stromal-immune cell communication in the tumor microenvironment by mediating the THBS2-CD47 and SPP1-CD44 interaction pathways, thereby promoting the progression of CRC.
