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血清骨桥蛋白水平和基因多态性作为生物标志物的评估:来自北欧辅助性α干扰素黑色素瘤试验的分析

Evaluation of serum osteopontin level and gene polymorphism as biomarkers: analyses from the Nordic Adjuvant Interferon alpha Melanoma trial.

作者信息

Prasmickaite Lina, Berge Gisle, Bettum Ingrid J, Aamdal Steinar, Hansson Johan, Bastholt Lars, Øijordsbakken Miriam, Boye Kjetil, Mælandsmo Gunhild M

机构信息

Division of Cancer, Surgery and Transplantation, Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0310, Montebello, Oslo, Norway,

出版信息

Cancer Immunol Immunother. 2015 Jun;64(6):769-76. doi: 10.1007/s00262-015-1686-4. Epub 2015 Apr 2.

Abstract

Malignant melanoma is highly aggressive cancer with poor prognosis and few therapeutic options. Interferon alpha (IFN-α) has been tested as adjuvant immunotherapy in high-risk melanoma patients in a number of studies, but its beneficial role is controversial. Although IFN-α treatment can prolong relapse-free survival, the effect on overall survival is not significant. However, a small subset of patients benefits from the treatment, signifying the need for biomarkers able to identify a responding subgroup. Here we evaluated whether serum osteopontin (OPN) could function as a biomarker identifying patients with poor prognosis that might benefit from IFN-α. The choice of osteopontin was based on the knowledge about the dual role of this protein in cancer and immune response, an apparent association between OPN and IFN signaling and a prognostic value of OPN in multiple other tumor types. Serum samples from 275 high-risk melanoma patients enrolled in the Nordic Adjuvant IFN Melanoma trial were analyzed for circulating OPN concentrations and OPN promoter polymorphisms in position -443. The potential relation between serum OPN levels, the genotypes and survival in non-treated patients and patients receiving adjuvant IFN-α was investigated. Although slightly better survival was observed in the treated patients that had high levels of OPN, the difference was not statistically significant. In conclusion, serum OPN (its level or the genotype) cannot distinguish melanoma patients with poor prognosis, or patients that might benefit from adjuvant treatment with IFN-α.

摘要

恶性黑色素瘤是一种侵袭性很强的癌症,预后较差,治疗选择有限。在多项研究中,已对干扰素α(IFN-α)作为高危黑色素瘤患者的辅助免疫疗法进行了测试,但其有益作用存在争议。虽然IFN-α治疗可延长无复发生存期,但对总生存期的影响并不显著。然而,一小部分患者从该治疗中获益,这表明需要能够识别有反应亚组的生物标志物。在此,我们评估了血清骨桥蛋白(OPN)是否可作为一种生物标志物,用于识别预后较差且可能从IFN-α中获益的患者。选择骨桥蛋白是基于对该蛋白在癌症和免疫反应中的双重作用、OPN与IFN信号传导之间明显关联以及OPN在多种其他肿瘤类型中的预后价值的了解。对参加北欧辅助性IFN黑色素瘤试验的275例高危黑色素瘤患者的血清样本进行分析,检测循环OPN浓度和-443位OPN启动子多态性。研究了血清OPN水平、基因型与未治疗患者及接受辅助性IFN-α治疗患者生存情况之间的潜在关系。虽然在OPN水平较高的治疗患者中观察到生存情况略好,但差异无统计学意义。总之,血清OPN(其水平或基因型)无法区分预后较差的黑色素瘤患者,或可能从IFN-α辅助治疗中获益的患者。

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