Department of Oncology, Changhai Hospital, Second Military Medical University, Changhai Road 168, Shanghai 200433, People's Republic of China.
J Cancer Res Clin Oncol. 2010 Oct;136(10):1617-26. doi: 10.1007/s00432-010-0819-6. Epub 2010 Feb 14.
Constitutive activation of JAK/STAT pathway is observed in various solid tumors and hematological malignancies. SOCS3 acts as a key negative regulator of JAK/STAT pathway and represents one of the candidate tumor suppressor genes. In the current study, we aimed to evaluate SOCS3 expression in breast carcinoma and to explore the prognostic significance of SOCS3.
The expression of SOCS3 was measured by Western blot and immunohistochemistry in breast carcinoma cells and a large cohort of tissue microarray, respectively.
Among 367 human primary breast tumors, SOCS3 protein was detected in 103 patients. Deficient SOCS3 expression correlated significantly with lymph node metastasis (P = 0.003), blood vessel invasion (P = 0.029), VEGF (P = 0.001) and Ki-67 (P = 0.027). Univariate and multivariate analyses revealed that SOCS3 expression was an independent prognostic factor for disease-free survival (P < 0.0001). A positive SOCS3 protein expression correlated significantly with a low pSTAT3 protein expression in breast carcinoma (P = 0.015). The patients with a SOCS3 (+)/pSTAT3 (-) phenotype had a better prognosis than any other combination (DFI: P < 0.0001, BCSS: P = 0.013).
Deficient expression of SOCS3 is associated with an aggressive phenotype and portends a poor clinical outcome in breast carcinoma.
JAK/STAT 通路的组成性激活在各种实体瘤和血液恶性肿瘤中均有观察到。SOCS3 作为 JAK/STAT 通路的关键负调控因子，代表候选肿瘤抑制基因之一。在本研究中，我们旨在评估 SOCS3 在乳腺癌中的表达，并探讨 SOCS3 的预后意义。
通过 Western blot 和免疫组织化学法分别在乳腺癌细胞和大量组织微阵列中检测 SOCS3 的表达。
在 367 例原发性乳腺癌中，有 103 例患者检测到 SOCS3 蛋白。SOCS3 表达缺失与淋巴结转移（P=0.003）、血管侵犯（P=0.029）、VEGF（P=0.001）和 Ki-67（P=0.027）显著相关。单因素和多因素分析显示，SOCS3 表达是无病生存的独立预后因素（P<0.0001）。SOCS3 蛋白阳性表达与乳腺癌中低 pSTAT3 蛋白表达显著相关（P=0.015）。SOCS3（+）/pSTAT3（-）表型的患者比任何其他组合的预后都要好（DFI：P<0.0001，BCSS：P=0.013）。
SOCS3 表达缺失与侵袭性表型相关，并预示乳腺癌患者的临床结局不良。
