Ottaviano Margaret, Giuliano Mario, Tortora Marianna, La Civita Evelina, Liotti Antonietta, Longo Michele, Bruzzese Dario, Cennamo Michele, Riccio Vittorio, De Placido Pietro, Picozzi Fernanda, Parola Sara, Daniele Bruno, Botti Gerardo, Formisano Pietro, Beguinot Francesco, De Placido Sabino, Terracciano Daniela, Palmieri Giovannella
Department of Clinical Medicine and Surgery, Università degli Studi di Napoli "Federico II", Naples, Italy.
CRCTR Rare Tumors Coordinating Center of Campania Region, Naples, Italy.
Front Oncol. 2021 Feb 4;10:602153. doi: 10.3389/fonc.2020.602153. eCollection 2020.
Thymic epithelial tumors (TETs) are rare thoracic malignancies, commonly divided into two different histopathological entities, thymoma (T) and thymic carcinoma (TC). To date, there are no specific biomarkers for monitoring the biological course of these rare tumors. We carried out a single center study aiming at the detection of circulating cell-free DNA (ccfDNA) and the correlation of its levels with metastatic dissemination and histological subtype in patients with TETs.
From July 2018 to January 2020, 5-ml blood samples from 26 patients with advanced TET (aTET) (11 patients with TC and 15 patients with T) and from six patients with completely resected TET (cr-TET), were prospectively obtained before the initiation of systemic therapy. Blood samples from 10 healthy donors were used as control. The QIAamp MinElute ccfDNA Kits was used for ccfDNA isolation from plasma; real-time PCR was used for cfDNA quantification.
We found significantly higher ccfDNA amount in patients with T and TC compared to controls, with median ccfDNA level of 3.3 ng/µl, 11.4 ng/µl and 25.6 ng/µl, for healthy donors, T and TC patients, respectively (p<0.001). No significant difference was found between cr-TET and controls (p = 0.175). ccfDNA concentrations were higher in metastatic (M1a and M1b) compared to non-metastatic (M0) TETs (25.6 ng/µl versus 7.2 ng/µl; p= 0.037). No significant correlation was found either between ccfDNA and disease stage, according to both the Masaoka-Koga (p= 0.854) and the TNM 8th edition staging systems (p = 0.66), or between ccfDNA levels and overall tumor burden, estimated according RECIST 1.1 criteria (r = 0.07, p = 0.725).
To the best of our knowledge, this is the first study that prospectively explores detection and quantification of ccfDNA in TETs. Higher baseline cfDNA levels have been observed in both advanced T and TC comparing to the control group.
胸腺上皮肿瘤（TETs）是罕见的胸部恶性肿瘤，通常分为两种不同的组织病理学类型，即胸腺瘤（T）和胸腺癌（TC）。迄今为止，尚无用于监测这些罕见肿瘤生物学进程的特异性生物标志物。我们开展了一项单中心研究，旨在检测循环游离DNA（ccfDNA）及其水平与TETs患者转移扩散和组织学亚型的相关性。
2018年7月至2020年1月，前瞻性地收集了26例晚期TET（aTET）患者（11例TC患者和15例T患者）以及6例完全切除的TET（cr-TET）患者在开始全身治疗前的5毫升血样。10名健康供者的血样用作对照。使用QIAamp MinElute ccfDNA试剂盒从血浆中分离ccfDNA；采用实时荧光定量PCR对cfDNA进行定量分析。
我们发现，与对照组相比，T和TC患者的ccfDNA量显著更高，健康供者、T患者和TC患者的ccfDNA中位数水平分别为3.3 ng/µl、11.4 ng/µl和25.6 ng/µl（p<0.001）。cr-TET与对照组之间未发现显著差异（p = 0.175）。与非转移性（M0）TET相比，转移性（M1a和M1b）TET的ccfDNA浓度更高（25.6 ng/µl对7.2 ng/µl；p = 0.037）。根据Masaoka-Koga分期系统（p = 0.854）和TNM第8版分期系统（p = 0.66），ccfDNA与疾病分期之间均未发现显著相关性，根据RECIST 1.1标准估计，ccfDNA水平与总体肿瘤负荷之间也未发现显著相关性（r = 0.07，p = 0.725）。
据我们所知，这是第一项前瞻性探索TETs中ccfDNA检测和定量的研究。与对照组相比，晚期T和TC患者均观察到更高的基线cfDNA水平。
