CXCL13/CXCR5 Axis Predicts Poor Prognosis and Promotes Progression Through PI3K/AKT/mTOR Pathway in Clear Cell Renal Cell Carcinoma
CXCL13/CXCR5 Axis Predicts Poor Prognosis and Promotes Progression Through PI3K/AKT/mTOR Pathway in Clear Cell Renal Cell Carcinoma
复制标题
CXCL13/CXCR5 轴通过 PI3K/AKT/mTOR 通路预测透明细胞肾细胞癌的不良预后并促进进展
DOI：
10.3389/fonc.2018.00682
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发表时间：
2019-01-22
影响因子：
4.7
通讯作者：
Xie, Wenlian
中科院分区：
文献类型：
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作者：
Zheng, Zaosong;Cai, Yuhong;Xie, Wenlian
趋化因子配体及其受体在癌症进展和患者预后中发挥着关键作用。我们发现，在癌症基因组图谱 (TCGA) 队列和经过验证的 90 对 ccRCC 组织队列中，与正常组织相比，ccRCC 组织中 CXCL13 显着上调。统计分析显示CXCL13高表达与ccRCC疾病分期晚期和不良预后相关。我们还发现，ccRCC 患者 (n = 50) 的血清 CXCL13 水平显着高于健康对照 (n = 40)。受试者工作特征 (ROC) 曲线显示，组织和血清 CXCL13 表达可能是 ccRCC 的诊断生物标志物，曲线下面积 (AUC) 分别为 0.809 和 0.704。 ccRCC组织中CXCL13与其受体CXCR5显着相关，CXCL13高CXCR5表达组的ccRCC患者预后最差。功能和机制研究表明，CXCL13通过与CXCR5结合并激活PI3K/AKT/mTOR信号通路促进ccRCC细胞的增殖和迁移。这些结果表明 CXCL13/CXCR5 轴在 ccRCC 中发挥重要作用，可能是治疗靶点和预后生物标志物。
The chemokine ligands and their receptors play critical roles in cancer progression and patients outcomes. We found that CXCL13 was significantly upregulated in ccRCC tissues compared with normal tissues in both The Cancer Genome Atlas (TCGA) cohort and a validated cohort of 90 pairs ccRCC tissues. Statistical analysis showed that high CXCL13 expression related to advanced disease stage and poor prognosis in ccRCC. We also revealed that serum CXCL13 levels in ccRCC patients (n = 50) were significantly higher than in healthy controls (n = 40). Receiver operating characteristic (ROC) curve revealed that tissue and serum CXCL13 expression might be a diagnostic biomarker for ccRCC with an area under curve (AUC) of 0.809 and 0.704, respectively. CXCL13 was significantly associated with its receptor, CXCR5, in ccRCC tissues, and ccRCC patients in high CXCL13 high CXCR5 expression group have a worst prognosis. Functional and mechanistic study revealed that CXCL13 promoted the proliferation and migration of ccRCC cells by binding to CXCR5 and activated PI3K/AKT/mTOR signaling pathway. These results suggested that CXCL13/CXCR5 axis played a significant role in ccRCC and might be a therapeutic target and prognostic biomarker.