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细胞因子信号传导抑制蛋白表达的意义:细胞因子信号传导抑制因子-1、细胞因子信号传导抑制因子-2和细胞因子信号传导抑制因子-3在甲状腺乳头状癌中的表达

Significance of expression of suppressor of cytokine signaling proteins: Suppressor of cytokine signaling-1, suppressor of cytokine signaling-2, and suppressor of cytokine signaling-3 in papillary thyroid cancer.

作者信息

Kobawala Toral Pundrik, Trivedi Trupti I, Gajjar Kinjal Kevin, Patel Girish H, Ghosh Nandita R

机构信息

Division of Molecular Endocrinology, Department of Cancer Biology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India.

出版信息

J Cancer Res Ther. 2017 Apr-Jun;13(2):337-345. doi: 10.4103/0973-1482.174172.

Abstract

PURPOSE

Uncontrolled cytokine signal transduction largely associated with oncogene activation, can have disastrous biological consequences. The suppressor of cytokine signaling (SOCS) proteins represent one of the mechanisms by which this rampant signaling can be dissipated. Thus, we aimed to study the expression of SOCS-1, SOCS-2, and SOCS-3 in patients having benign thyroid disease and papillary thyroid cancer.

MATERIALS AND METHODS

SOCS protein expression was studied in 45 patients with benign thyroid disease and in 83 papillary thyroid cancer patients by immunohistochemistry and their association with clinicopathological characteristics and overall survival in cancer patients were analyzed using SPSS software.

RESULTS

Expressions of SOCS proteins were significantly higher in papillary thyroid cancer than in patients having benign disease. SOCS-1 expression was predominantly higher in males (P = 0.004), unilateral tumors (P = 0.030), and noninflammatory conditions (P = 0.028). SOCS-1 expression was also able to predict poor overall survival in subgroup of papillary thyroid cancer patients having larger tumor size (P = 0.013) and advanced stage disease (P = 0.033). Expression of SOCS-2 significantly correlated with tumor size (P = 0.017), extrathyroidal extension (P = 0.000), residual disease (P = 0.043), and treatment (P = 0.007), while preponderance of SOCS-3 expression was observed in males (P = 0.030) and in patients having extrathyroidal extension (P = 0.011) and absence of metastasis (P = 0.032).

CONCLUSION

Expression of the studied SOCS proteins may be a consequence of activation of Janus kinase-signal transducers and activators of transcription and other pathways supporting growth and survival of cancer cells that are sustained by several cytokines. Thus, SOCS-1, SOCS-2, and SOCS-3 proteins may directly or indirectly, have important roles in development and pathogenesis of papillary thyroid cancer.

摘要

目的

不受控制的细胞因子信号转导在很大程度上与癌基因激活相关,可能会产生灾难性的生物学后果。细胞因子信号转导抑制因子(SOCS)蛋白是消散这种失控信号的机制之一。因此,我们旨在研究细胞因子信号转导抑制因子-1(SOCS-1)、细胞因子信号转导抑制因子-2(SOCS-2)和细胞因子信号转导抑制因子-3(SOCS-3)在患有良性甲状腺疾病和甲状腺乳头状癌患者中的表达情况。

材料与方法

采用免疫组织化学方法研究了45例良性甲状腺疾病患者和83例甲状腺乳头状癌患者中SOCS蛋白的表达情况,并使用SPSS软件分析了其与癌症患者临床病理特征及总生存期的相关性。

结果

甲状腺乳头状癌中SOCS蛋白的表达明显高于良性疾病患者。SOCS-1的表达在男性(P = 0.004)、单侧肿瘤(P = 0.030)和非炎症状态(P = 0.028)中占主导地位且更高。在肿瘤体积较大(P = 0.013)和疾病分期较晚(P = 0.033)的甲状腺乳头状癌患者亚组中,SOCS-1的表达也能够预测较差的总生存期。SOCS-2的表达与肿瘤大小(P = 0.017)、甲状腺外扩展(P = 0.000)、残留病灶(P = 0.043)及治疗(P = 0.007)显著相关,而SOCS-3的表达在男性(P = 0.030)、有甲状腺外扩展的患者(P = 0.011)及无转移的患者(P = 0.032)中占优势。

结论

所研究的SOCS蛋白的表达可能是由几种细胞因子维持的支持癌细胞生长和存活的Janus激酶-信号转导子和转录激活子及其他途径激活的结果。因此,SOCS-1、SOCS-2和SOCS-3蛋白可能直接或间接在甲状腺乳头状癌的发生发展和发病机制中发挥重要作用。

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