Vihinen Pia, Tervahartiala Taina, Sorsa Timo, Hansson Johan, Bastholt Lars, Aamdal Steinar, Stierner Ulrika, Pyrhönen Seppo, Syrjänen Kari, Lundin Johan, Hernberg Micaela
Department of Oncology and Radiotherapy, Turku University Hospital, POB 52, 20521, Turku, Finland,
Cancer Immunol Immunother. 2015 Feb;64(2):173-80. doi: 10.1007/s00262-014-1620-1. Epub 2014 Oct 16.
Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre-treatment sera from 460 patients with stage IIB-IIIC melanoma were analyzed for MMP-8. The patients were randomized after surgery to adjuvant IFN-α for 12 or 24 months (n = 313) or observation only (n = 147). The median serum MMP-8 level was used to classify the patients into a low MMP-8 (n = 232) and a high MMP-8 (n = 228) group. In the high MMP-8 subgroup, IFN-α therapy significantly improved relapse-free survival (RFS). RFS was 36.8 months in patients with high MMP-8 levels receiving IFN-α therapy, whereas RFS for those with high MMP-8 levels with observation only was 10.6 months (P = 0.027). Median overall survival for patients with high MMP-8 and observation only was 36.7 versus 71.7 months in those receiving IFN-α (P = 0.13). In a multivariate model, IFN-α therapy was a significant predictor of favorable RFS (HR 0.74; 95 % CI 0.55-0.99; P = 0.048), after adjustment for pre-treatment MMP-8 (HR 1.17; 95 % CI 0.88-1.55; P = 0.28), gender (HR 1.16; 95 % CI 0.86-1.56; P = 0.32), age (HR 1.00; 95 % CI 1.00-1.02; P = 0.12), ulceration (HR 1.09; 95 % CI 0.81-1.46; P = 0.58), and the presence of node metastases (HR 1.36; 95 % CI 1.17-1.58; P < 0.0001). In conclusion, patients with high serum MMP-8 levels may benefit from adjuvant IFN-α therapy, but this observation should be further investigated.
基质金属蛋白酶（MMPs）是组织更新和各种炎症过程中的重要酶类。在本研究中，评估了血清MMP - 8是否能够预测接受手术治疗的高危皮肤黑色素瘤患者对辅助性干扰素α - 2b（IFN-α）治疗的反应。对460例IIB - IIIC期黑色素瘤患者的治疗前血清进行MMP - 8分析。患者术后被随机分为接受12个月或24个月辅助性IFN-α治疗组（n = 313）或仅观察组（n = 147）。采用血清MMP - 8水平中位数将患者分为低MMP - 8组（n = 232）和高MMP - 8组（n = 228）。在高MMP - 8亚组中，IFN-α治疗显著改善了无复发生存期（RFS）。接受IFN-α治疗的高MMP - 8水平患者的RFS为36.8个月，而仅接受观察的高MMP - 8水平患者的RFS为10.6个月（P = 0.027）。仅接受观察的高MMP - 8水平患者的总生存期中位数为36.7个月，而接受IFN-α治疗的患者为71.7个月（P = 0.13）。在多变量模型中，在对治疗前MMP - 8（HR 1.17；95%CI 0.88 - 1.55；P = 0.28）、性别（HR 1.16；95%CI 0.86 - 1.56；P = 0.32）、年龄（HR 1.00；95%CI 1.00 - 1.02；P = 0.12）、溃疡（HR 1.09；95%CI 0.81 - 1.46；P = 0.58）以及淋巴结转移情况（HR 1.36；95%CI 1.17 - 1.58；P < 0.0001）进行校正后，IFN-α治疗是RFS良好的显著预测因素（HR 0.74；95%CI 0.55 - 0.99；P = 0.048）。总之，血清MMP - 8水平高的患者可能从辅助性IFN-α治疗中获益，但这一观察结果应进一步研究。
