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通过抗体阵列鉴定肿瘤微环境中的趋化因子 CXCL10 作为肝细胞癌的预后标志物。

Identification of chemokine CXCL10 in tumor microenvironment by antibody array as a prognostic marker in hepatocellular carcinoma.

出版信息

Neoplasma. 2017;64(5):778-786. doi: 10.4149/neo_2017_517.

DOI:10.4149/neo_2017_517
PMID:28592115
Abstract

Immunological microenvironment is not only composed of multiple immune cells, but also deposited various inflammation factors that regulate immune response to tumor cells. To ascertain the crucial immune factors presented in hepatocellular carcinoma microenvironment (HCM), tumor tissue culture supernatant (TCS) and the corresponding non-tumor tissue culture supernatant (NCS) from patient with hepatocellular carcinoma (HCC) were analyzed by antibody array technology. Among the inflammation-associated cytokines assayed, high level of chemokines CXCL8/IL-8 (6.82-fold increase) and CXCL10/IP-10 (16.45-fold increase) in TCS than that in paired NCS were evidently identified. And low expression of IL-16 (0.14-fold decrease) and RANTES/CCL5 (0.17-fold decrease) in TCS were also uncovered. Especially, overexpression of CXCL10 in primary HCC compared with their non-tumor counterparts was significantly associated with serum AFP level (P = 0.004), tumor size (P = 0.021), tumor number (P < 0.001) and TNM stage (P = 0.027). In addition, Kaplan-Meier curves demonstrated that patients with higher CXCL10 expression levels had significantly poorer overall survival (P = 0.016) and disease-free survival (P = 0.022) than those with lower CXCL10 expression levels. Univariate and multivariate analyses revealed that the level of CXCL10 expression was an independent prognostic factor for overall survival in HCC patients. In summary, high concentration of CXCL10 is deposited in HCM identified by antibody array, which may contribute to the prediction of clinical outcome of HCC patients.

摘要

免疫微环境不仅由多种免疫细胞组成,还沉积着各种调节免疫细胞对肿瘤细胞应答的炎症因子。为了确定肝癌微环境(HCM)中关键的免疫因子,我们采用抗体芯片技术分析了肝癌患者肿瘤组织培养上清液(TCS)和相应的非肿瘤组织培养上清液(NCS)。在所检测的炎症相关细胞因子中,TCS 中趋化因子 CXCL8/IL-8(增加 6.82 倍)和 CXCL10/IP-10(增加 16.45 倍)的水平明显高于配对的 NCS。TCS 中 IL-16(减少 0.14 倍)和 RANTES/CCL5(减少 0.17 倍)的表达也较低。特别是,与非肿瘤组织相比,原发性 HCC 中 CXCL10 的过表达与血清 AFP 水平(P = 0.004)、肿瘤大小(P = 0.021)、肿瘤数量(P < 0.001)和 TNM 分期(P = 0.027)显著相关。此外,Kaplan-Meier 曲线表明,CXCL10 表达水平较高的患者总生存期(P = 0.016)和无病生存期(P = 0.022)明显低于 CXCL10 表达水平较低的患者。单因素和多因素分析表明,CXCL10 表达水平是 HCC 患者总生存期的独立预后因素。综上所述,抗体芯片鉴定出 HCM 中 CXCL10 浓度较高,可能有助于预测 HCC 患者的临床结局。

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