Favorable prognostic value of SOCS2 and IGF-I in breast cancer.
Favorable prognostic value of SOCS2 and IGF-I in breast cancer.
复制标题
SOCS2和IGF-I在乳腺癌中的有利预后价值。
DOI：
10.1186/1471-2407-7-136
复制
发表时间：
2007-07-25
期刊：
影响因子：
3.8
通讯作者：
Doppler, Wolfgang
中科院分区：
文献类型：
--
作者：
Haffner, Michael C.;Petridou, Barbara;Peyrat, Jean Phillipe;Revillion, Francoise;Mueller-Holzner, Elisabeth;Daxenbichler, Guenter;Marth, Christian;Doppler, Wolfgang
细胞因子信号转导抑制因子(SoCs)蛋白是一个蛋白质家族，最初被描述为STAT诱导的Jak/Stat途径的抑制因子。最近的体内和体外研究表明，SOCS蛋白也与癌症有关。STAT5诱导的IGF-I在乳腺发育中作为内分泌和类/自分泌生长分化因子发挥作用。虽然高水平的循环IGF-I与癌症风险增加有关，但自分泌作用于IGF-I的作用尚不清楚。本研究旨在探讨乳腺癌中SOCS1、SOCS2、SOCS3、CIS和IGF-I表达的临床病理特征。采用逆转录聚合酶链式反应(RT-PCR)检测89例乳腺癌组织中SOCS1、SOCS2、SOCS3、CIS和IGF-I的mRNA表达水平。免疫印迹和免疫组织化学方法进一步检测SOCS2蛋白的表达。SOCS2的表达与组织学分级呈负相关，ER阳性肿瘤的SOCS2表达水平较高。SOCS2高表达患者生存期显著延长(108.7个月vs.77.7月；P=0.015)，高SOCS2表达是预后良好的独立预测因素(HR=0.45，95%CI0.23~0.91，P=0.026)。与SOCS2类似，在整个患者队列中，IGF-I的高表达是预后良好的独立预测因子。在淋巴结阴性患者亚组中，高胰岛素样生长因子-I是总生存期和无复发生存期良好的预测因子(HR=0.075，95%CI 0.014~0.388，P=0.002)。这是首次报道SOCS2高表达在乳腺癌中的良好预后价值。此外，观察到IGF-I的高表达水平与良好的预后密切相关，尤其是在淋巴结阴性的患者中。我们的结果表明，STAT5靶基因SOCS2和IGF-I的高表达是分化和较低恶性度肿瘤的一个特征。
Suppressor of cytokine signaling (SOCS) proteins comprise a protein family, which has initially been described as STAT induced inhibitors of the Jak/Stat pathway. Recent in vivo and in vitro studies suggest that SOCS proteins are also implicated in cancer. The STAT5 induced IGF-I acts as an endocrine and para/autocrine growth and differentiation factor in mammary gland development. Whereas high levels of circulating IGF-I have been associated with increased cancer risk, the role of autocrine acting IGF-I is less clear. The present study is aimed to elucidate the clinicopathological features associated with SOCS1, SOCS2, SOCS3, CIS and IGF-I expression in breast cancer. We determined the mRNA expression levels of SOCS1, SOCS2, SOCS3, CIS and IGF-I in 89 primary breast cancers by reverse transcriptase PCR. SOCS2 protein expression was further evaluated by immuno-blot and immunohistochemistry. SOCS2 expression inversely correlated with histopathological grade and ER positive tumors exhibited higher SOCS2 levels. Patients with high SOCS2 expression lived significantly longer (108.7 vs. 77.7 months; P = 0.015) and high SOCS2 expression proved to be an independent predictor for good prognosis (HR = 0.45, 95% CI 0.23 – 0.91, P = 0.026). In analogy to SOCS2, high IGF-I expression was an independent predictor for good prognosis in the entire patient cohort. In the subgroup of patients with lymph-node negative disease, high IGF-I was a strong predictor for favorable outcome in terms of overall survival and relapse free survival (HR = 0.075, 95% CI 0.014 – 0.388, P = 0.002). This is the first report on the favorable prognostic value of high SOCS2 expression in primary mammary carcinomas. Furthermore a strong association of high IGF-I expression levels with good prognosis was observed especially in lymph-node negative patients. Our results suggest that high expression of the STAT5 target genes SOCS2 and IGF-I is a feature of differentiated and less malignant tumors.
登录
查看更多内容
影响因子：
3.4
作者：
Farabegoli, F;Ceccarelli, C;Taffurelli, M
通讯作者：
Taffurelli, M
影响因子：
4.8
作者：
Leong, GM;Moverare, S;Leung, KC
通讯作者：
Leung, KC
影响因子：
9.8
作者：
Marth, C;Fiegl, H;Daxenbichler, G
通讯作者：
Daxenbichler, G
影响因子：
11.2
作者：
Hendriksen, Peter J. M.;Dits, Natasja F. J.;Jenster, Guido
通讯作者：
Jenster, Guido
影响因子：
20.3
作者：
Galm, O;Yoshikawa, H;Herman, JG
通讯作者：
Herman, JG