The role of CXCL chemokine family in the development and progression of gastric cancer.
The role of CXCL chemokine family in the development and progression of gastric cancer.
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发表时间：
2020-03
影响因子：
1.4
通讯作者：
Xuyan Chen;Renpin Chen;Ruifang Jin;Zhiming Huang
中科院分区：
文献类型：
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作者：
Xuyan Chen;Renpin Chen;Ruifang Jin;Zhiming Huang
趋化因子（C-X-C基序）配体（CXCL）家族在炎症中起重要作用。为了了解CXC趋化因子家族在癌变中的作用，本研究对一组早期胃癌（GC）患者进行了研究，评估了代表体循环和肿瘤微环境的患者血液样本中CXC趋化因子配体（CXCL）的水平，检测了肿瘤组织中CXC趋化因子受体（CXCR）的表达，并测量了肿瘤浸润免疫细胞亚群。69例胃癌患者纳入单中心前瞻性研究，随访6年。ELISA法检测CXCL1-14水平，计算趋化因子浓度梯度。Western blot检测肿瘤组织中CXCR1、CXCR2、CXCR3、CXCR4的表达。通过siRNA抑制CXCL1-14在HGC27细胞中的表达，然后通过细胞划痕试验检测HGC27细胞的迁移能力。本研究结果显示，治疗后无复发患者外周血及肿瘤引流血中CXCL1、CXCL2、CXCL5、CXCL8、CXCL11、CXCL13趋化因子浓度均显著低于治疗前。外周血及肿瘤引流血中CXCL1、CXCL2、CXCL4、CXCL5、CXCL7、CXCL8、CXCL9、CXCL10、CXCL12、CXCL13、CXCL14的浓度均显著高于无复发患者。CXCR1和CXCR3低表达的患者AFP（甲胎蛋白）较低，肿瘤体积较小，肿瘤分期TNM较低。CXCR2和CXCR4表达水平较低的患者AFP （α胎蛋白）水平较高，肿瘤体积较大，肿瘤分期TNM较高。下调CXCLs表达后，大多数细胞系的迁移能力明显受到抑制。本研究提示CXCL趋化因子家族在胃癌发病中起重要作用，可作为胃癌发展的标志物。
The chemokine (C-X-C motif) ligand (CXCL) family plays an important role in inflammation. In order to understand the role of CXC chemokine family in carcinogenesis, this study explored a group of early gastric cancer (GC) patients, and assessed the level of CXC chemokine ligand (CXCL) in blood samples of patients representing systemic circulation and tumor microenvironment, detected the expression of CXC chemokine receptor (CXCR) in tumor tissues, and measured tumor infiltrating immune cell subsets. 69 patients with GC were included in a single center prospective study and were followed up for 6 years. The level of CXCL1-14 was determined by ELISA and the concentration gradient of chemokine was calculated. Western blot was used to detect the expression of CXCR1, CXCR2, CXCR3, and CXCR4 in tumor tissue. CXCL1-14 expression was inhibited by siRNA in HGC27 cells and then the migration ability of HGC27 cells was detected by cell scratch test. The results of this study showed that the chemokine concentrations of CXCL1, CXCL2, CXCL5, CXCL8, CXCL11, and CXCL13 in peripheral blood and tumor drainage blood of patients without recurrence after treatment were significantly lower than those before treatment. The concentrations of CXCL1, CXCL2, CXCL4, CXCL5, CXCL7, CXCL8, CXCL9, CXCL10, CXCL12, CXCL13, and CXCL14 in peripheral blood and tumor drainage blood were significantly higher than those in patients without recurrence. Patients with low expression of CXCR1 and CXCR3 had lower AFP (alpha fetoprotein), smaller tumor volume, and lower TNM tumor stage. Patients with lower expression of CXCR2 and CXCR4 had higher AFP (alpha fetoprotein) level, larger tumor volume, and higher TNM tumor stage. After down-regulation of CXCLs expression, the migration ability of most cell lines was significantly inhibited. This study suggests that CXCL chemokine family plays an important role in the pathogenesis of GC and can be used as a marker for the development of GC.