CCR6 Is a Predicting Biomarker of Radiosensitivity and Potential Target of Radiosensitization in Rectal Cancer.
CCR6 Is a Predicting Biomarker of Radiosensitivity and Potential Target of Radiosensitization in Rectal Cancer.
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CCR6是直肠癌放射敏感性的预测生物标志物和放射增敏的潜在靶点
DOI：
10.4143/crt.2017.538
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发表时间：
2018-10
影响因子：
4.6
通讯作者：
Xiao WW
中科院分区：
文献类型：
--
作者：
Chang H;Wei JW;Tao YL;Ding PR;Xia YF;Gao YH;Xiao WW
目的探讨结直肠癌（CRC）进展转移相关基因C-C基序趋化因子受体6 （CCR6）在直肠癌（RC）放射敏感性中的作用及机制。材料与方法对不同放疗效果的RC患者预处理组织进行RNA测序和CCR6表达的免疫组化分析。在不同的结直肠癌细胞系中进行结肠菌存活试验，以评估其放射敏感性。通过RNA干扰验证CCR6表达对放射敏感性的影响。采用免疫荧光法定量测定不同CCR6表达细胞系的DNA损伤修复（DDR）能力。结果无病理完全缓解（pCR）患者CCR6 mRNA水平高于有病理完全缓解（pCR）患者（翻倍变化，2.11;p=0.004）。CCR6蛋白的高水平表达在不良应答者中比在良好应答者中更常见（76.3%比37.5%,p < 0.001）。与CCR6表达水平较低的sw620细胞系相比，CCR6表达水平较高的CRC细胞系（LoVo和sw480）表现出更强的耐辐射能力。CCR6敲低使LoVo细胞对电离辐射更加敏感（敏化增强比为1.738,p < 0.001），并降低了其DDR效率。结论CCR6可能通过DDR过程影响RC的放射敏感性。这些发现支持CCR6作为预测放射敏感性的生物标志物和RC患者放射增敏的潜在靶点。
Purpose This study aimed to explore the functions and mechanisms of C-C motif chemokine receptor 6 (CCR6), a gene associated with progression and metastasis of colorectal cancer (CRC), in radiosensitivity of rectal cancer (RC). Materials and Methods RNA sequencing and immunohistochemical analysis on CCR6 expression were performed in pretreatment tissues of RC patients exhibiting different therapeutic effects of radiotherapy. Colonogenic survival assay was conducted in different CRC cell lines to assess their radiosensitivity. And the impact of CCR6 expression on radiosensitivity was validated through RNA interference. The DNA damage repair (DDR) abilities of cell lines with different CCR6 expression were evaluated through immunofluorescence-based γH2AX quantification. Results The CCR6 mRNA level was higher in patients without pathologic complete remission (pCR) than in those with pCR (fold changed, 2.11; p=0.004). High-level expression of CCR6 protein was more common in the bad responders than in the good responders (76.3% vs. 37.5%, p < 0.001). The CRC cell lines with higher CCR6 expression (LoVo and sw480) appeared to be more radioresistant, compared with the sw620 cell line which had lower CCR6 expression. CCR6 knockdown made the LoVo cells more sensitive to ionizing radiation (sensitization enhancement ratio, 1.738; p < 0.001), and decreased their DDR efficiency. Conclusion CCR6 might affect the RC radiosensitivity through DDR process. These findings supported CCR6 as a predicting biomarker of radiosensitivity and a potential target of radiosensitization for RC patients.
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影响因子：
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作者：
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