de Lecea M V, Palomares T, Al Kassam D, Cavia M, Geh J L C, de Llano P, Muñiz P, Armesto D, Martinez-Indart L, Alonso-Varona A
Cruces University Hospital, Osakidetza, Biscay, Spain.
University of the Basque Country UPV/EHU, Biscay, Spain.
J Eur Acad Dermatol Venereol. 2017 Apr;31(4):636-642. doi: 10.1111/jdv.13968. Epub 2016 Oct 10.
To date, lactate dehydrogenase (LDH) and S100B remain the most useful biomarkers for follow-up of melanoma patients. In recent years, indoleamine 2,3-dioxygenase (IDO), an immunosuppressive enzyme, has been proposed as a new potential tumour biomarker for melanoma. However, further studies are needed to confirm the usefulness of IDO expression as an independent prognostic factor.
To explore the potential association between serum IDO levels and melanoma stage at diagnosis and recurrence, and to compare the results to those obtained with LDH and S100B. In addition, we also investigated a possible cut off for IDO level as a prognostic factor for overall survival.
IDO, LDH and S100B levels were measured in serum samples of 186 patients in all melanoma stages at diagnosis and twice a year thereafter. A cut-off point for IDO levels was calculated using receiver operating characteristic curves to explore the association between these levels and the likelihood of lymphatic spread. Survival curves were estimated for patient groups stratified by IDO level (higher or lower than the cut off), using the Kaplan-Meier method.
At diagnosis, serum IDO levels were significantly higher in stages IB, II, III and IV, whereas S100B levels were significantly higher in stages III and IV, and LDH levels were only higher in stage IV. In relapsed patients, significant increases were found in levels of all three markers. Finally, overall survival was significantly longer in patients with IDO levels below a cut off of 1.65 μM at diagnosis than in those with higher levels (91.3 vs. 71.0% at 36 months).
In melanoma patients, serum IDO levels are significantly associated with disease stage, relapses and overall survival. These results indicate IDO could be a useful serum prognostic marker for melanoma.
迄今为止，乳酸脱氢酶（LDH）和S100B仍然是黑色素瘤患者随访中最有用的生物标志物。近年来，吲哚胺2,3-双加氧酶（IDO），一种免疫抑制酶，已被提议作为黑色素瘤的一种新的潜在肿瘤生物标志物。然而，需要进一步研究以证实IDO表达作为独立预后因素的有用性。
探讨血清IDO水平与黑色素瘤诊断及复发时分期之间的潜在关联，并将结果与LDH和S100B的结果进行比较。此外，我们还研究了IDO水平作为总生存预后因素的可能临界值。
在186例处于所有黑色素瘤分期的患者诊断时及其后每年两次采集的血清样本中检测IDO、LDH和S100B水平。使用受试者工作特征曲线计算IDO水平的临界值，以探讨这些水平与淋巴转移可能性之间的关联。使用Kaplan-Meier方法为按IDO水平（高于或低于临界值）分层的患者组估计生存曲线。
诊断时，IB期、II期、III期和IV期患者的血清IDO水平显著更高，而III期和IV期患者的S100B水平显著更高，LDH水平仅在IV期更高。在复发患者中，所有三种标志物的水平均显著升高。最后，诊断时IDO水平低于1.65 μM临界值的患者的总生存期显著长于水平较高的患者（36个月时为91.3%对71.0%）。
在黑色素瘤患者中，血清IDO水平与疾病分期、复发及总生存显著相关。这些结果表明IDO可能是黑色素瘤一种有用的血清预后标志物。
