CCR5 通路的潜在分子串扰预测转移性结直肠癌患者对regorafenib 的反应。
Potential Molecular Cross Talk Among CCR5 Pathway Predicts Regorafenib Responsiveness in Metastatic Colorectal Cancer Patients.
机构信息
Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, U.S.A.;
Gastroenterology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
出版信息
Cancer Genomics Proteomics. 2021 May-Jun;18(3):317-324. doi: 10.21873/cgp.20262.
Abstract
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.
摘要
背景
CCL5/CCR5 通路中的遗传变异已被证明可预测转移性结直肠癌（mCRC）患者接受regorafenib 治疗的疗效。本研究探讨了 CCL4 和 CCL3 基因多态性在接受regorafenib 治疗的难治性 mCRC 患者中的生物学作用。
患者和方法
我们分析了接受regorafenib 治疗的 mCRC 患者提取的基因组 DNA。使用 ELISA 测定基线、第 21 天和进展性疾病（PD）时的血清因子水平。
结果
第 21 天 CCL4 水平降低或 PD 时 CCL3 水平升高与更好的临床结局相关。在任何 CCL5 rs2280789 G 等位基因的患者中，与 A/A 变异相比，CCL3 在 BL 和第 21 天之间显著增加（72.7%比 23.1%，p=0.006），但 CCL4 降低（31.8%比 69.2%，p=0.043）。
结论
在特定基因型中观察到的 CCL3 增加和 CCL4 减少可能是 mCRC 患者接受regorafenib 治疗的潜在生物标志物。
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2
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Tumour Biol. 2018 Nov;40(11):1010428318810059. doi: 10.1177/1010428318810059.
3
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8
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10
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