ArticleTechnology in cancer research & treatment2018
Prediction of Target Genes and Pathways Associated With Cetuximab Insensitivity in Colorectal Cancer.
Article in Technology in cancer research & treatment, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Biochemical pharmacology of adenylyl cyclases in cancer.Biochemical pharmacology · 2024Review
- Antitumor Effect of Poplar Propolis on Human Cutaneous Squamous Cell Carcinoma A431 Cells.International journal of molecular sciences · 2023Article
- ACACB is a novel metabolism-related biomarker in the prediction of response to cetuximab therapy inmetastatic colorectal cancer.Acta biochimica et biophysica Sinica · 2022Article
- Targeting Adenylate Cyclase Family: New Concept of Targeted Cancer Therapy.Frontiers in oncology · 2022Review
- GNG4 Promotes Tumor Progression in Colorectal Cancer.Journal of oncology · 2021Article
- Predicting Panel of Metabolism and Immune-Related Genes for the Prognosis of Human Ovarian Cancer.Frontiers in cell and developmental biology · 2021Article
- Characterisation of the Expression of Neurotensin and Its Receptors in Human Colorectal Cancer and Its Clinical Implications.Biomolecules · 2020Article
- A novel prognostic signature of immune-related genes for patients with colorectal cancer.Journal of cellular and molecular medicine · 2020Article
- Association between liver targeted antiviral therapy in colorectal cancer and survival benefits: An appraisal.World journal of clinical cases · 2020Review
- Identification of key pathways and genes in colorectal cancer to predict the prognosis based on mRNA interaction network.Oncology letters · 2019Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCetuximab has been regularly added to the treatments for metastatic colorectal cancer worldwide. However, due to its therapeutic insensitivity and underlying mechanisms being largely unknown, the clinical implementation of cetuximab in colorectal cancer remains limited.
methodsThe gene expression profile GSE56386 was retrieved from the Gene Expression Omnibus database. Differentially expressed genes were identified between cetuximab-responsive patients and nonresponders, annotated by gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and further analyzed by protein-protein interaction networks. The integrative prognostic analysis was based on The Cancer Genome Atlas and PrognoScan.
results1350 differentially expressed genes were identified with 298 upregulated and 1052 downregulated. Epidermis development, the cornified envelope, calcium ion binding, and amoebiasis were enriched in upregulated genes while digestion, the apical part of the cell, the 3',5'-cyclic-adenosine monophosphate phosphodiesterase activity and pancreatic secretion were found enriched in downregulated genes. The top 10 hub genes were identified, including epithermal growth factor, G-protein subunit β 5, G-protein subunit γ 4, fibroblast growth factor 2, B-cell lymphoma protein 2, acetyl-coenzyme A carboxylase β, KIT proto-oncogene receptor tyrosine kinase, adenylate cyclase 4, neuropeptide Y, and neurotensin. The hub genes exhibited distinct correlations in cetuximab-treated and untreated genomic profiles (GSE56386, GSE5851 and GSE82236). The highest correlation was found between B-cell lymphoma protein 2 and acetyl-coenzyme A carboxylase β in GSE56386. The mRNA expression of hub genes was further validated in the genomic profile GSE65021. Furthermore, B-cell lymphoma protein 2 and acetyl-coenzyme A carboxylase β also exhibited highest degrees among the hub genes correlation networks based on The Cancer Genome Atlas. Both B-cell lymphoma and acetyl-coenzyme A carboxylase β were not independent prognostic factors for colorectal cancer in univariate and multivariate Cox analysis. However, integrative survival analysis indicated that B-cell lymphoma protein 2 was associated with favorable prognosis (hazard ratio = 0.62, 95% confidence interval, 0.30-0.95, P = .024). DISCUSSION: This in silico analysis provided a feasible and reliable strategy for systematic exploration of insightful target genes, pathways and mechanisms underlying the cetuximab insensitivity in colorectal cancer. B-cell lymphoma protein 2 was associated with favorable prognosis.
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