SHP2 associates with nuclear localization of STAT3: significance in progression and prognosis of colorectal cancer.
SHP2 associates with nuclear localization of STAT3: significance in progression and prognosis of colorectal cancer.
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SHP2 与 STAT3 核定位相关：在结直肠癌进展和预后中的意义
DOI：
10.1038/s41598-017-17604-7
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发表时间：
2017-12-14
影响因子：
4.6
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Huang Y;Wang J;Cao F;Jiang H;Li A;Li J;Qiu L;Shen H;Chang W;Zhou C;Pan Y;Lu Y
由PTPN 11编码的酪氨酸磷酸酶SHP 2参与肿瘤进展中的许多生理和病理过程。然而，许多研究中出现了争议，表明SHP 2在不同类型的肿瘤中具有双重作用。本研究旨在探讨SHP 2在结直肠癌（CRC）进展和预后中的作用。SHP 2可抑制结直肠癌细胞的增殖和迁移，并负调控STAT 3的磷酸化。检测270例大肠癌组织中SHP 2和STAT 3的表达。SHP 2与核STAT 3显着相关（斯皮尔曼rho =-0.408，P ≤ 0.001）。基于考克斯回归分析，具有高水平的SHP 2和低水平的核STAT 3的患者具有较长的疾病特异性生存期（DSS）（HR，0.362; 95%CI，0.165-0.794）和无病生存期（DFS）（HR，0.447; 95%CI，0.227-0.877）。此外，低水平的SHP 2和高水平的核STAT 3与整个队列中的不良结局独立相关（DFS; HR，2.353; 95%CI，1.199-4.619）。这些结果表明，SHP 2和核STAT 3的组合是CRC的强预后预测因子。
Tyrosine phosphatase SHP2, encoded by PTPN11, has been implicated in many physiologic and pathologic processes in neoplastic progression. However, controversies are emerging from many studies, indicating SHP2 has a dual role in different types of tumors. We aimed to explore the role of SHP2 in progression and prognosis of colorectal cancer (CRC). SHP2 inhibited CRC cell proliferation and migration, and the phosphorylation of STAT3 was negatively regulated by SHP2 in CRC. SHP2 and nuclear STAT3 were examined in 270 CRC tissues. SHP2 was significantly correlated with nuclear STAT3 (Spearman’s rho = −0.408, P ≤ 0.001). Based on Cox regression analysis, patients with high levels of SHP2 and low levels of nuclear STAT3 had longer disease-specific survival (DSS) (HR, 0.362; 95% CI, 0.165–0.794) and disease-free survival (DFS) (HR, 0.447; 95% CI, 0.227–0.877). Further, low levels of SHP2 and high levels of nuclear STAT3 were independently associated with adverse outcomes in the whole cohort (DFS; HR, 2.353; 95% CI, 1.199–4.619). These results suggest that combination of SHP2 and nuclear STAT3 is a strong prognostic predictor in CRC.
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