Expression of SOCSs in human prostate cancer and their association in prognosis
Expression of SOCSs in human prostate cancer and their association in prognosis
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DOI：
10.1007/s11010-013-1687-6
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发表时间：
2013-05
影响因子：
4.3
通讯作者：
Jian-guo Zhu;Q. Dai;Zhao‐dong Han;Hui‐chan He;R. Mo;Guo Chen;Yan-fei Chen;Yong-ding Wu;
中科院分区：
文献类型：
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作者：
Jian-guo Zhu;Q. Dai;Zhao‐dong Han;Hui‐chan He;R. Mo;Guo Chen;Yan-fei Chen;Yong-ding Wu;
细胞因子信号传导抑制因子（SOCS）蛋白已被确定为多种组织中细胞因子介导的信号传导的负反馈调节因子，并被证明在不同癌症的肿瘤发生和肿瘤发展中发挥关键作用。SOCSs在人类前列腺癌（PCa）中的作用尚未完全阐明。因此，本研究的目的是探讨SOCSs在PCa中的表达模式及其临床意义。采用实时定量逆转录-聚合酶链式反应（QRT-PCR）和免疫组织化学方法检测SOCSs在人前列腺癌组织中mRNA和蛋白水平的表达变化。进一步统计分析SOCSs表达与PCa患者临床病理特征及临床转归的关系。QRT-PCR和免疫组化分析发现，与非癌前列腺组织相比，PCa组织中SOCS2表达上调（mRNA水平变化比为1.98，P= 0.031；蛋白水平变化比为5.12±0.60，P= 2.68±0.37，P= 0.016）， SOCS6表达下调（mRNA水平变化比为- 1.65，P= 0.008；蛋白水平变化比为3.03±0.32，P= 4.0.72±0.39，P= 0.004）。此外，PCa组织中SOCS2表达上调与较低的Gleason评分（P< 0.001）、无转移（P< 0.001）和PSA阴性失败（P= 0.009）相关；SOCS6表达下调倾向于Gleason评分越高（P= 0.016）、病理分期越晚期（P= 0.007）、转移阳性（P= 0.020）、PSA失败阳性（P= 0.032）的前列腺癌组织。此外，单因素和多因素分析均表明，SOCS2的下调是缩短生化无复发生存期的独立预测因子。我们的数据首次提供了令人信服的证据，证明SOCS2和SOCS6的失调可能与PCa的侵袭性进展有关。SOCS2可能是PCa患者预后的潜在标志物。
Suppressors of cytokine signaling (SOCS) proteins have been identified as negative feedback regulators of cytokine-mediated signaling in various tissues, and demonstrated to play critical roles in tumorigenesis and tumor development of different cancers. The involvement of SOCSs in human prostate cancer (PCa) has not been fully elucidated. Thus, the aim of this study is to investigate the expression patterns and the clinical significance of SOCSs in PCa. The expression changes of SOCSs at mRNA and protein levels in human PCa tissues compared with adjacent benign prostate tissues were, respectively, detected by using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and immunohistochemistry analyses. The associations of SOCSs expression with clinicopathological features and clinical outcome of PCa patients were further statistically analyzed. Among SOCSs, both QRT-PCR and immunohistochemistry analyses found that SOCS2 expression was upregulated (at mRNA level: change ratio = 1.98,P= 0.031; at protein level: 5.12 ± 0.60 vs. 2.68 ± 0.37,P= 0.016) and SOCS6 expression was downregulated (at mRNA level: change ratio = −1.65,P= 0.008; at protein level: 3.03 ± 0.32 vs. 4.0.72 ± 0.39,P= 0.004) in PCa tissues compared with those in non-cancerous prostate tissues. In addition, the upregulation of SOCS2 in PCa tissues was correlated with the lower Gleason score (P< 0.001), the absence of metastasis (P< 0.001) and the negative PSA failure (P= 0.009); the downregulation of SOCS6 tended to be found in PCa tissues with the higher Gleason score (P= 0.016), the advanced pathological stage (P= 0.007), the positive metastasis (P= 0.020), and the positive PSA failure (P= 0.032). Furthermore, both univariate and multivariate analyses showed that the downregulation of SOCS2 was an independent predictor of shorter biochemical recurrence-free survival. Our data offer the convincing evidence for the first time that the dysregulation of SOCS2 and SOCS6 may be associated with the aggressive progression of PCa. SOCS2 may be potential markers for prognosis in PCa patients.