Expression of SOCS1 and CXCL12 Proteins in Primary Breast Cancer Are Associated with Presence of Circulating Tumor Cells in Peripheral Blood.
Expression of SOCS1 and CXCL12 Proteins in Primary Breast Cancer Are Associated with Presence of Circulating Tumor Cells in Peripheral Blood.
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DOI：
10.1016/j.tranon.2016.03.004
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发表时间：
2016-06
影响因子：
5
通讯作者：
Fridrichova I
中科院分区：
文献类型：
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作者：
Smolkova B;Mego M;Horvathova Kajabova V;Cierna Z;Danihel L;Sedlackova T;Minarik G;Zmetakova I;Krivulcik T;Gronesova P;Karaba M;Benca J;Pindak D;Mardiak J;Reuben JM;Fridrichova I
循环肿瘤细胞（CTC）是乳腺癌原发灶和转移灶的独立预后因子，在肿瘤血行播散中起重要作用。本研究的目的是将外周血中CTC的存在与肿瘤组织中蛋白质的表达相关联，所述蛋白质在细胞生长和转移潜力的调节中具有推定的作用。这项前瞻性研究包括203例接受确定性手术治疗的原发性乳腺癌患者。通过定量实时PCR检测CTC的上皮（CK 19）或上皮-间充质转化诱导转录因子基因（TWIST 1、SNAIL 1、SLUG和ZEB 1）的表达。免疫组化检测APC、ADAM 23、CXCL 12、E-cadherin、RASSF 1、SYK、TIMP 3、BRMS 1和SOCS 1蛋白在原发性乳腺肿瘤组织中的表达。在17例（9.2%）患者中发现了具有上皮标志物的CTC。它们的发生与SOCS 1表达的抑制有关（比值比[OR] = 0.07; 95%置信区间[CI]，0.03-0.13; P <0.001）。在30例（15.8%）患者中检测到上皮-间质转化标志物阳性的CTC;然而，未发现与分析的蛋白表达相关。任何CTC标志物的存在与患者肿瘤组织中的阳性CXCL 12表达（OR = 3.08; 95%CI，1.15-8.26; P = .025）和缺乏SOCS 1表达（OR = 0.10; 95%CI，0.04-0.25; P < .001）显著相关。由于CXCL 12和SOCS 1蛋白都参与细胞因子信号传导，我们的研究结果为细胞因子和趋化因子反应之间的异常信号传导串扰可能在乳腺癌肿瘤细胞的血行播散中起重要作用的假设提供了支持。
Circulating tumor cells (CTCs) are independent prognostic factors in the primary and metastatic breast cancer patients and play crucial role in hematogenous tumor dissemination. The aim of this study was to correlate the presence of CTCs in peripheral blood with the expression of proteins in tumor tissue that have a putative role in regulation of cell growth and metastatic potential. This prospective study included 203 primary breast cancer patients treated by definitive surgery. CTCs were detected by quantitative real-time PCR for the expression of epithelial (CK19) or epithelial-to-mesenchymal transition–inducing transcription factor genes (TWIST1, SNAIL1, SLUG, and ZEB1). Expression of APC, ADAM23, CXCL12, E-cadherin, RASSF1, SYK, TIMP3, BRMS1, and SOCS1 proteins in primary breast tumor tissue was evaluated by immunohistochemistry. CTCs with epithelial markers were found in 17 (9.2%) patients. Their occurrence was associated with inhibition of SOCS1 expression (odds ratio [OR] = 0.07; 95% confidence interval [CI], 0.03-0.13; P < .001). CTCs with positive epithelial-to-mesenchymal transition markers were detected in 30 (15.8%) patients; however, no association with analyzed protein expressions was found. Overall, CTCs were detected in 44 (22.9%) patients. Presence of any CTC marker was significantly associated with positive CXCL12 expression (OR = 3.08; 95% CI, 1.15-8.26; P = .025) and lack of SOCS1 expression (OR = 0.10; 95% CI, 0.04-0.25; P < .001) in patient’s tumor tissues. As both CXCL12 and SOCS1 proteins are involved in cytokine signaling, our results provide support for the hypothesis that aberrant signaling cross talk between cytokine and chemokine responses could have an important role in hematogenous dissemination of tumor cells in breast cancer.