Potential Molecular Cross Talk Among CCR5 Pathway Predicts Regorafenib Responsiveness in Metastatic Colorectal Cancer Patients
Potential Molecular Cross Talk Among CCR5 Pathway Predicts Regorafenib Responsiveness in Metastatic Colorectal Cancer Patients
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DOI：
10.21873/cgp.20262
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发表时间：
2021-05-01
影响因子：
2.5
通讯作者：
Lenz, Heinz-Josef
中科院分区：
文献类型：
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作者：
Suenaga, Mitsukuni;Zhang, W. U.;Lenz, Heinz-Josef
背景资料：CCL 5/CCR 5通路中的遗传变异已被证明可预测瑞格非尼在转移性结直肠癌（mCRC）患者中的疗效。本研究探讨了CCL 4和CCL 3基因多态性在使用瑞戈非尼治疗的难治性mCRC患者中的生物学作用。患者和方法：我们分析了从接受瑞戈非尼治疗的mCRC患者中提取的基因组DNA。使用ELISA测量基线、第21天和疾病进展（PD）时的血清因子水平。结果：第21天CCL 4水平降低或PD时CCL 3水平升高与更好的临床结局相关。在具有任何CCL 5 rs 2280789 G等位基因的患者中，与A/A变体相比，CCL 3在BL和第21天之间显著增加（72.7%对23.1%，p=0.006），但CCL 4降低（31.8%对69.2%，p=0.043）。结论：在特定基因型中观察到的CCL 3升高和CCL 4降低可能是mCRC患者中瑞戈非尼的潜在生物标志物。
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.