Boerlin Aurelio, Bellini Elisa, Turko Patrick, Cheng Phil F, Levesque Mitchell P, Dummer Reinhard, Ramelyte Egle
Department of Dermatology, University Hospital Zurich, 8091 Zurich, Switzerland.
Medical Faculty, University of Zurich, 8006 Zurich, Switzerland.
Cancers (Basel). 2022 Aug 27;14(17):4158. doi: 10.3390/cancers14174158.
Melanoma currently lacks validated blood-based biomarkers for monitoring and predicting treatment efficacy. Circulating tumor DNA (ctDNA), originating from tumor cells and detectable in plasma, has emerged as a possible biomarker in patients with metastatic melanoma. In this retrospective, single-center study, we collected 129 plasma samples from 79 patients with stage IIIB-IV melanoma as determined by the American Joint Committee on Cancer (AJCC, 8th edition). For the determination of ctDNA levels, we used eight different assays of droplet digital polymerase chain reaction (ddPCR) to detect the most common hotspot mutations in the and genes. The aim of the study was to investigate the association of the detectability of ctDNA at a non-prespecified time point in a patient's treatment with tumor progression, and to correlate ctDNA with commonly used biomarkers (protein S100, LDH, and CRP). Patients with detectable ctDNA progressed more frequently in PET-CT within 12 months than those without detectable ctDNA. Detectability of ctDNA was associated with shorter OS in univariate and multivariate analyses. ctDNA was detectable in a statistically significantly larger proportion of patients with distant metastases (79%) than in patients with no distant metastases or only intracranial metastases (32%). Elevated protein S100 and CRP correlated better with detectable ctDNA than LDH. This study supports the potential of ctDNA as a prognostic biomarker in patients with metastatic melanoma. However, additional prospective longitudinal studies with quantitative assessments of ctDNA are necessary to investigate the limitations and strengths of ctDNA as a biomarker.
黑色素瘤目前缺乏经过验证的基于血液的生物标志物来监测和预测治疗效果。循环肿瘤DNA（ctDNA）源自肿瘤细胞，可在血浆中检测到，已成为转移性黑色素瘤患者可能的生物标志物。在这项回顾性单中心研究中，我们收集了79例美国癌症联合委员会（AJCC，第8版）确定的IIIB-IV期黑色素瘤患者的129份血浆样本。为了测定ctDNA水平，我们使用了八种不同的液滴数字聚合酶链反应（ddPCR）检测方法来检测 和 基因中最常见的热点突变。本研究的目的是调查患者治疗过程中在非预先指定时间点ctDNA的可检测性与肿瘤进展之间的关联，并将ctDNA与常用生物标志物（蛋白S100、乳酸脱氢酶和C反应蛋白）进行关联分析。ctDNA可检测的患者在12个月内PET-CT检查中进展的频率高于ctDNA不可检测的患者。在单变量和多变量分析中，ctDNA的可检测性与较短的总生存期相关。远处转移患者中ctDNA可检测的比例（79%）在统计学上显著高于无远处转移或仅有颅内转移的患者（32%）。与乳酸脱氢酶相比，蛋白S100和C反应蛋白升高与可检测的ctDNA相关性更好。本研究支持ctDNA作为转移性黑色素瘤患者预后生物标志物的潜力。然而，需要进行更多关于ctDNA定量评估的前瞻性纵向研究，以探讨ctDNA作为生物标志物的局限性和优势。
