Potential Molecular Cross Talk Among CCR5 Pathway Predicts Regorafenib Responsiveness in Metastatic Colorectal Cancer Patients
| Autor: | Toshiharu Yamaguchi, Shu Cao, Marta Schirripa, Martin D. Berger, Satoshi Okazaki, Mitsukuni Suenaga, Afsaneh Barzi, Tetsuo Mashima, Wu Zhang, Heinz-Josef Lenz, Yuji Miyamoto |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Male Cancer Research medicine.medical_specialty Receptors CCR5 Colorectal cancer Pyridines Single-nucleotide polymorphism Biochemistry CCL5 chemistry.chemical_compound Refractory Internal medicine Regorafenib Genotype parasitic diseases Genetics medicine Humans Allele Neoplasm Metastasis 610 Medicine & health Chemokine CCL4 Molecular Biology Aged Chemokine CCL3 Polymorphism Genetic business.industry Phenylurea Compounds Middle Aged medicine.disease digestive system diseases chemistry Female business Colorectal Neoplasms Progressive disease Research Article Signal Transduction |
| Zdroj: | Cancer Genomics Proteomics |
| Popis: | BACKGROUND Genetic variants in the CCL5/CCR5 pathway have been shown to predict regorafenib efficacy in patients with metastatic colorectal cancer (mCRC). This study investigated the biological role of CCL4 and CCL3 gene polymorphisms in patients with refractory mCRC treated using regorafenib. PATIENTS AND METHODS We analyzed the genomic DNA extracted from mCRC patients receiving regorafenib. Serum factor levels at baseline, day 21, and progressive disease (PD) were measured using ELISA. RESULTS Decreased CCL4 levels at day 21 or increased CCL3 levels at PD were associated with better clinical outcomes. In patients with any CCL5 rs2280789 G allele, CCL3 significantly increased between BL and day 21 compared with the A/A variant (72.7% vs. 23.1%, p=0.006), but CCL4 decreased (31.8% vs. 69.2%, p=0.043). CONCLUSION Increased CCL3 and decreased CCL4 seen in specific genotypes may serve as potential biomarkers of regorafenib in mCRC patients. |
| Databáze: | OpenAIRE |
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