Screening and Verification of Hub Genes in Colorectal Cancer Using Bioinformatics
Keywords:
Colorectal cancer, Bioinformatics, Hub genesAbstract
Objective: To screen differentially expressed genes (DEGs) associated with colorectal cancer using bioinformatics analysis and verify their biological functions. Methods: The Department of Clinical Laboratory at Yunfu People’s Hospital downloaded colorectal cancer microarray data (GSE21815, GSE31905, GSE35279) from the Gene Expression Omnibus (GEO). GEO2R was used to process the data and identify DEGs between colorectal cancer and normal colorectal tissues. Bioinformatics tools such as DAVID, STRING, and Cytoscape were utilized to construct a protein-protein interaction network for the DEGs, screen for hub genes, and analyze the biological functions of these hub genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Potential miRNAs regulating the hub genes were identified using MiRDB. Additionally, 30 colorectal cancer tissue samples and 30 normal colorectal tissue samples collected from August 2017 to August 2022 were used for validation through quantitative real-time PCR (qPCR). Results: The oxytocin receptor gene, matrix metalloproteinase-11 gene, mesenchymal-epithelial transition factor gene, matrix metalloproteinase-7 gene, kallikrein-8 gene, and kallikrein-10 gene were identified as key hub genes for the development and progression of colorectal cancer through bioinformatics analysis and protein-protein interaction network analysis. The expression levels of matrix metalloproteinase-11 gene (4.38 ± 1.58), mesenchymal-epithelial transition factor gene (2.69 ± 0.29), matrix metalloproteinase-7 gene (0.88 ± 0.14), kallikrein-8 gene (11.09 ± 3.90), and kallikrein-10 gene mRNA (7.88 ± 2.20) were significantly higher in colorectal cancer tissues compared to normal colorectal tissues, with statistically significant differences (t = 9.605, 25.339, 26.376, 9.541, 3.726; all P < 0.001). Conclusion: The abnormal expression of the matrix metalloproteinase-11 gene, mesenchymal-epithelial transition factor gene, matrix metalloproteinase-7 gene, kallikrein-8 gene, and kallikrein-10 gene in colorectal cancer tissues may be involved in the development of colorectal cancer, providing a basis for future basic research and clinical diagnosis and treatment of colorectal cancer.
References
Wang X, Liu Z, Gong H, et al., 2022, Advances in the Study of Biomarkers for Colorectal Cancer. Journal of Colorectal & Anal Surgery, 28(1): 34–38.
China Anti-Cancer Association, 2021, Targeted Therapy Committee. Expert Consensus on Molecular Testing for Colorectal Cancer Using High-Throughput Sequencing in China. Chinese Journal of Clinical Oncology, 26(3): 253–264.
Fan X, Shao C, Cui L, 2019, Prediction and Validation of Hub Genes in Colorectal Cancer Based on PPI Network Analysis. Chinese Journal of Medical Library and Information Science, 28(6): 17–25.
Yin X, Xue X, Zhao H, 2021, Bioinformatics Analysis for Screening Key Genes and Related Pathways in Gallbladder Cancer. Chinese Journal of Cancer Surgery, 13(1): 12–19.
Chen S, Ma T, Zhang Z, et al., 2022, Mechanism of Long Non-Coding RNA LINC01419 in Regulating Proliferation, Apoptosis, Migration, and Invasion of Colorectal Cancer Cells. Anhui Medical and Pharmaceutical Journal, 26(3): 572–577, Cover 3.
Zhao L, Han T, Li K, et al., 2023, Differential Analysis of Genes and Proteins Related to Carcinogenesis in Colon and Rectal Cancer. Beijing Medicine, 45(4): 284–288.
Gong H, Huang X, Chen H, et al., 2022, Research Progress on Epigenetic Biomarkers for Colorectal Cancer. Journal of Colorectal & Anal Surgery, 28(1): 14–18.
Yi M, Lü S, Du Q, et al., 2022, Value of Combined Detection of MMP-11 and Macrophage Inhibitory Cytokine-1 in the Diagnosis and Prognosis Assessment of Colorectal Cancer. Cancer Progress, 20(5): 505–507, 512.
Shi C, Cheng J, Liu H, et al., 2023, Expression and Clinical Value of SPOCK1, MMP11, and MMP9 in Colorectal Cancer. Chongqing Medicine, 52(1): 102–107.
Chen W, 2021, Value of Detecting MMP-7 Expression by Immunohistochemistry in Assessing Safe Surgical Margins for Rectal Cancer. Heilongjiang Medicine, 34(3): 708–709.
Luo S, Li T, 2022, Application Value of Serum MMP-11 and Angiopoietin-2 in Diagnosing Colorectal Cancer. Basic and Clinical Oncology, 35(3): 198–200.
Li J, Chen W, Li Z, et al., 2022, Expression of MMP7, CD44v7, Survivin, and PPARγ in Serum of Colorectal Cancer Patients and Its Clinical Significance. Practical Oncology Journal, 37(7): 1068–1071.
Wen L, Wang Q, Mai Q, et al., 2023, Expression of Five Genes in Stool mRNA and Their Clinical Significance in Colorectal Cancer Patients. Journal of Clinical Digestive Diseases, 35(4): 301–306.
Fan G, Liang X, Gao B, et al., 2021, Relationship Between c-MET, CXCR4 Proteins, and Microvessel Density in Colorectal Cancer with Liver Metastasis. Tumor Research and Clinical, 33(11): 830–833.
Cao M, Huai J, Yang X, 2023, Application Value of MACC1, c-Met, and ERCC1 Expression in Pathological Assessment of Colorectal Cancer. Contemporary Medicine Symposium, 21(9): 5–9.
Li X, Zheng J, Yao R, et al., 2016, Research Progress on Prognostic Value of Human Tissue Kallikrein in Colorectal Cancer Patients. Shandong Medicine, 56(34): 99–102.
Hua Q, Shen X, Xu P, 2021, Mechanism of KLK8 in Regulating Colorectal Cancer Cell Apoptosis via EGF. Chinese Cancer Journal, 31(5): 383–389.
Guo P, He N, Xia Y, 2021, Data Mining Analysis of Human Tissue Kallikrein Family in Colorectal Cancer Expression and Prognosis. Cancer Progress, 19(2): 149–153, 177.