Elevated levels of circulating IL-7 and IL-15 in patients with early stage prostate cancer
Elevated levels of circulating IL-7 and IL-15 in patients with early stage prostate cancer
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DOI：
10.1186/1479-5876-9-162
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发表时间：
2011-09-26
影响因子：
7.4
通讯作者：
Wyler, Stephen
中科院分区：
文献类型：
--
作者：
Mengus, Chantal;Le Magnen, Clementine;Wyler, Stephen
背景：慢性炎症被认为有利于前列腺癌(PCA)的发展。白细胞介素2(IL)是一种重要的炎症介质。IL-2、IL-7、IL-15和IL-21共享一个共同的受体g链(c-g)，控制T淋巴细胞的动态平衡和增殖，在调节肿瘤-免疫系统的相互作用中发挥重要作用。我们检测了早期前列腺癌和良性前列腺增生症(BPH)患者前列腺组织中IL-2、IL-7、IL-15和IL-21基因的表达。作为对照，我们使用了IL-6基因，它编码了一种参与PCa进展的IL。方法：对80例BPH患者和79例早期(1~2c)前列腺癌患者进行血清IL-6、IL-7和IL-15检测。用实时定量聚合酶链式反应(qRT-PCR)分析前列腺组织中基因的表达。采用双抗体夹心法测定血清IL浓度和急性时相蛋白滴度。用Mann-Whitney、Wilcoxon和chi(2)检验比较两组患者的IL基因表达和血清滴度。结果：IL-2和IL-21基因在PCa和BPH组织中的表达频率较低，且表达程度较低。与之相比，IL-6、IL-7和IL-15基因在早期PCa组织中的表达频率较高(p<；0.0001，p=0.0047和p=0.0085)，且表达程度显著高于良性前列腺增生症组织(p=0.0051，p=0.0310和p=0.0205)。局限性前列腺癌患者血清中相应蛋白的含量显著高于良性前列腺增生症患者(p=0.0153，p=0.0174和p=0.0064)。ROC曲线分析表明，IL-7(p=0.0039)，而不是IL-6(p=0.2938)或IL-15(p=0.1804)滴度能够区分良恶性疾病患者的血清。两组患者血清C反应蛋白(CRP)、高迁移率族B1(HMGB1)和血清淀粉样蛋白A(SAA)急性时相蛋白滴度相似。结论：早期PCa患者前列腺组织中IL-7和IL-15基因的表达及相应的血清滴度明显高于BPH患者。
Background: Chronic inflammation has been suggested to favour prostate cancer (PCA) development. Interleukins (IL) represent essential inflammation mediators. IL-2, IL-7, IL-15 and IL-21, sharing a common receptor g chain (c-g), control T lymphocyte homeostasis and proliferation and play major roles in regulating cancer-immune system interactions. We evaluated local IL-2, IL-7, IL-15 and IL-21 gene expression in prostate tissues from patients with early stage PCA or benign prostatic hyperplasia (BPH). As control, we used IL-6 gene, encoding an IL involved in PCA progression. IL-6, IL-7 and IL-15 titres were also measured in patients' sera.Methods: Eighty patients with BPH and 79 with early (1 to 2c) stage PCA were enrolled. Gene expression in prostate tissues was analyzed by quantitative real-time PCR (qRT-PCR). Serum IL concentrations and acute phase protein titres were evaluated by ELISA. Mann-Whitney, Wilcoxon and chi(2) tests were used to compare IL gene expression and serum titers in the two groups of patients. Receiver operating characteristic (ROC) curves were constructed to evaluate the possibility to distinguish sera from different groups of patients based on IL titers.Results: IL-2 and IL-21 gene expression was comparably detectable, with low frequency and at low extents, in PCA and BPH tissues. In contrast, IL-6, IL-7 and IL-15 genes were expressed more frequently (p < 0.0001, p = 0.0047 and p = 0.0085, respectively) and to significantly higher extents (p = 0.0051, p = 0.0310 and p = 0.0205, respectively) in early stage PCA than in BPH tissues. Corresponding proteins could be detected to significantly higher amounts in sera from patients with localized PCA, than in those from patients with BPH (p = 0.0153, p = 0.0174 and p = 0.0064, respectively). Analysis of ROC curves indicates that IL-7 (p = 0.0039), but not IL-6 (p = 0.2938) or IL-15 (p = 0.1804) titres were able to distinguish sera from patients with malignancy from those from patients with benign disease. Serum titres of C reactive (CRP), high mobility group B1 (HMGB1) and serum amyloid A (SAA) acute phase proteins were similar in both groups of patients.Conclusions: Expression IL-7 and IL-15 genes in prostate tissues and corresponding serum titres are significantly increased in patients with early stage PCA as compared with patients with BPH.