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切梅宁在可切除非小细胞肺癌中作为炎症、趋化、凝血、纤溶和代谢交汇点的生物标志物。

Chemerin as a biomarker at the intersection of inflammation, chemotaxis, coagulation, fibrinolysis and metabolism in resectable non-small cell lung cancer.

机构信息

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527 Athens, Greece; Department of Thoracic Surgery, 'Sotiria' General Hospital, 152 Mesogeion Avenue, 11527 Athens, Greece.

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527 Athens, Greece.

出版信息

Lung Cancer. 2018 Nov;125:291-299. doi: 10.1016/j.lungcan.2018.10.010. Epub 2018 Oct 10.

Abstract

OBJECTIVES

Chemerin is an emerging adipocytokine at the intersection of inflammation, chemotaxis, thrombosis, fibrinolysis and metabolism. Our aims were 1) to explore circulating chemerin in resectable non-small cell lung cancer (NSCLC) taking into account its several interfaces; 2) to study its diagnostic potential; and 3) to assess its associations with clinicopathological features of NSCLC.

MATERIALS AND METHODS

In a large case-control study, serum chemerin, insulin resistance and lipid parameters, classic adipocytokines, inflammatory, coagulation, fibrinolysis and tumor biomarkers were determined in 110 consecutive patients with resectable NSCLC and 110 healthy controls matched on age (± 5 years), gender and date of blood draw (± 1 month).

RESULTS

NSCLC cases exhibited significantly elevated circulating chemerin compared to controls (p < 0.001). In NSCLC cases, chemerin was positively associated with Homeostasis model assessment score of insulin resistance (HOMA-IR), fibrinogen, plasminogen activity, tumor and inflammatory biomarkers, adiponectin, number of infiltrated lymph nodes and NSCLC stage. In control participants, circulating chemerin was positively correlated with somatometric, metabolic, lipid, hemostatic and inflammatory biomarkers, and leptin. Serum chemerin was independently associated with NSCLC, above and beyond NSCLC risk factors (OR: 2.20, 95% CI: 1.09-4.40, p = 0.03). In cases, hemostatic parameters (platelet count and plasminogen activity), HOMA-IR, CYFRA 21-1, creatinine and plant food consumption emerged as independent predictors of circulating chemerin (p < 0.05). Serum chemerin greater than 220 μg/L (cut-off point) yielded a sensitivity and a specificity of 63% and 91.8% respectively with a modest discriminative ability (AUC = 0.72, 95% C.I. 0.64-0.79) for the diagnosis of NSCLC.

CONCLUSION

Chemerin may represent a potentially useful biomarker in NSCLC integrating tumor-promoting networks, inflammatory and hemostatic mechanisms, and cancer-related metabolic pathways. More preclinical, prospective and longitudinal studies highlighting the pathogenetic role of chemerin in NSCLC are needed to corroborate and extend these data.

摘要

目的

趋化素是一种新兴的脂肪细胞因子,位于炎症、趋化、血栓形成、纤溶和代谢的交汇处。我们的目的是 1)在考虑其多个界面的情况下,研究可切除的非小细胞肺癌(NSCLC)中的循环趋化素;2)研究其诊断潜力;3)评估其与 NSCLC 临床病理特征的相关性。

材料和方法

在一项大型病例对照研究中,对 110 例连续的可切除 NSCLC 患者和 110 例年龄(±5 岁)、性别和采血日期(±1 个月)匹配的健康对照者的血清趋化素、胰岛素抵抗和脂质参数、经典脂肪细胞因子、炎症、凝血、纤溶和肿瘤标志物进行了测定。

结果

与对照组相比,NSCLC 患者的循环趋化素显著升高(p<0.001)。在 NSCLC 患者中,趋化素与胰岛素抵抗的稳态模型评估评分(HOMA-IR)、纤维蛋白原、纤溶酶原活性、肿瘤和炎症标志物、脂联素、浸润淋巴结数量和 NSCLC 分期呈正相关。在对照组中,循环趋化素与人体测量、代谢、脂质、止血和炎症标志物以及瘦素呈正相关。血清趋化素与 NSCLC 相关,独立于 NSCLC 危险因素(OR:2.20,95%CI:1.09-4.40,p=0.03)。在病例中,止血参数(血小板计数和纤溶酶原活性)、HOMA-IR、CYFRA 21-1、肌酐和植物性食物摄入是循环趋化素的独立预测因子(p<0.05)。血清趋化素大于 220μg/L(截断值)对 NSCLC 的诊断具有 63%的敏感性和 91.8%的特异性,并且具有适度的鉴别能力(AUC=0.72,95%CI:0.64-0.79)。

结论

趋化素可能代表一种有用的 NSCLC 生物标志物,整合了促肿瘤网络、炎症和止血机制以及癌症相关的代谢途径。需要更多的临床前、前瞻性和纵向研究来证实和扩展这些数据,以强调趋化素在 NSCLC 中的发病机制作用。

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