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CC趋化因子配体18和胰岛素样生长因子结合蛋白6作为前列腺癌潜在的血清生物标志物。

CC chemokine ligand 18 and IGF-binding protein 6 as potential serum biomarkers for prostate cancer.

作者信息

Xu Yong, Zhang Lei, Sun Sheng-kun, Zhang Xu

机构信息

Department of Urology, PLA General Hospital.

出版信息

Tohoku J Exp Med. 2014 May;233(1):25-31. doi: 10.1620/tjem.233.25.

Abstract

Prostate cancer (PCa) is the second leading cause of cancer-related death in men globally. However, there are few sensitive biomarkers for PCa, especially those which can distinguish PCa and benign prostate hyperplasia (BPH). Antibody microarrays allow for high-throughput and high-sensitivity detection of multiple proteins simultaneously, providing a powerful tool for biomarker screening. Here, we selected 46 patients with PCa and 42 controls with BPH, and compared the serum levels of different cytokines in PCa and BPH patients using antibody microarrays. The results indicated that serum levels of macrophage colony-stimulating factor (M-CSF) and CC chemokine ligand 18 (CCL-18) were remarkably higher in PCa patients than those in BPH patients, while serum levels of insulin-like growth factor-binding protein 6 (IGFBP-6) and Fas receptor (Fas), also called tumor necrosis factor receptor superfamily member 6 (TNFRSF6), were significantly lower. M-CSF and Fas/TNFRSF6 have been reported to be associated with PCa pathogenesis, and thus were used as positive controls in the present study. CCL-18 is a chemokine primarily involved in recruitment of the adaptive immune system, while IGFBP-6 has been reported to inhibit proliferation of PCa cells. Serum levels of these four cytokines could distinguish PCa from BPH with high sensitivity and high specificity. Furthermore, the area under the ROC curve (AUC) was above 0.925 and 0.835 for CCL-18 and IGFBP-6, respectively, implying their high diagnostic value. In conclusion, we have identified CCL-18 and IGFBP-6 as new potential serum biomarkers for PCa.

摘要

前列腺癌(PCa)是全球男性癌症相关死亡的第二大主要原因。然而,针对PCa的敏感生物标志物很少,尤其是那些能够区分PCa和良性前列腺增生(BPH)的标志物。抗体微阵列允许同时对多种蛋白质进行高通量和高灵敏度检测,为生物标志物筛选提供了强大工具。在此,我们选取了46例PCa患者和42例BPH对照患者,使用抗体微阵列比较了PCa患者和BPH患者血清中不同细胞因子的水平。结果表明,PCa患者血清中巨噬细胞集落刺激因子(M-CSF)和CC趋化因子配体18(CCL-18)的水平显著高于BPH患者,而胰岛素样生长因子结合蛋白6(IGFBP-6)和Fas受体(Fas,也称为肿瘤坏死因子受体超家族成员6,TNFRSF6)血清水平则显著较低。据报道,M-CSF和Fas/TNFRSF6与PCa发病机制相关,因此在本研究中用作阳性对照。CCL-18是一种主要参与适应性免疫系统募集的趋化因子,而据报道IGFBP-6可抑制PCa细胞增殖。这四种细胞因子的血清水平能够以高灵敏度和高特异性区分PCa和BPH。此外,CCL-18和IGFBP-6的ROC曲线下面积(AUC)分别高于0.925和0.835,这意味着它们具有较高的诊断价值。总之,我们已将CCL-18和IGFBP-6鉴定为PCa新的潜在血清生物标志物。

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