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Expression of Tumor-Related Macrophages and Cytokines After Surgery of Triple-Negative Breast Cancer Patients and its Implications

机译:三阴性乳腺癌患者手术后肿瘤相关巨噬细胞和细胞因子的表达及其意义

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BACKGROUND Triple-negative breast cancer (TNBC) has negative expression of progesterone receptor (PR) and estrogen receptor (ER), and low expression of human epithelial growth factor receptor-2 (HER-2). This study aimed to investigate the expressional profile of cytokines in TNBC patients with significant expression of macrophages. MATERIAL AND METHODS Immunohistochemical (IHC) S-P staining method was used to detect the tumor-associated macrophages (TAMs) marker CD68 expression in 48 cases of TNBC samples. The correlation between CD68 expression and prognosis was analyzed. Expressions of key cytokines – interleukin-6 (IL-6), IL-10, IL-12, IL-1β, chemokine (C-C motif) ligand-5 (CCL-5), and macrophage inflammatory protein-2 (MIP-2) – were quantified by RT-PCR and enzyme-linked immunosorbent assay (ELISA). RESULTS Thirty-four out of 48 TNBC samples (71.4%) had CD68-positive expression. IL-6 and CCL-5 were up-regulated in high-infiltrated tumors when compared to low-infiltrated samples. Other cytokines had no significant difference regarding the expression level across groups. CONCLUSIONS TAMs were up-regulated in most TNBC patients after the surgery. Its expression suggested unfavorable prognosis, especially in the high-infiltrated group. Those tumors with more macrophage also had elevated expression of cytokine IL-6 and chemotactic factor CCL-5, both of which have potency to be clinical index and drug target for TNBC.
机译:背景技术三阴性乳腺癌(TNBC)具有孕激素受体(PR)和雌激素受体(ER)的阴性表达,以及人上皮生长因子受体2(HER-2)的低表达。这项研究旨在调查在巨噬细胞大量表达的TNBC患者中细胞因子的表达情况。材料与方法采用免疫组织化学(IHC)S-P染色法检测48例TNBC样品中肿瘤相关巨噬细胞(TAMs)标记CD68的表达。分析了CD68表达与预后之间的相关性。关键细胞因子的表达–白介素6(IL-6),IL-10,IL-12,IL-1β,趋化因子(CC基序)配体5(CCL-5)和巨噬细胞炎性蛋白2(MIP-2) )–通过RT-PCR和酶联免疫吸附测定(ELISA)进行定量。结果48个TNBC样本中有34个(71.4%)具有CD68阳性表达。与低浸润样本相比,IL-6和CCL-5在高浸润肿瘤中上调。其他细胞因子之间的表达水平没有显着差异。结论手术后大多数TNBC患者的TAM均被上调。其表达提示预后不良,特别是在高浸润组中。那些具有更多巨噬细胞的肿瘤也具有细胞因子IL-6和趋化因子CCL-5的表达升高,两者均具有作为TNBC的临床指标和药物靶标的潜力。

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