Casas-Arozamena Carlos, Díaz Eva, Moiola Cristian Pablo, Alonso-Alconada Lorena, Ferreirós Alba, Abalo Alicia, Gil Carlos López, Oltra Sara S, de Santiago Javier, Cabrera Silvia, Sampayo Victoria, Bouso Marta, Arias Efigenia, Cueva Juan, Colas Eva, Vilar Ana, Gil-Moreno Antonio, Abal Miguel, Moreno-Bueno Gema, Muinelo-Romay Laura
Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela (IDIS), University Hospital of Santiago de Compostela (SERGAS), Trav. Choupana s/n, 15706 Santiago de Compostela, Spain.
Foundation MD Anderson International, C/Gómez Hemans 2, 28033 Madrid, Spain.
J Clin Med. 2020 Feb 21;9(2):585. doi: 10.3390/jcm9020585.
The incidence and mortality of endometrial cancer (EC) have risen in recent years, hence more precise management is needed. Therefore, we combined different types of liquid biopsies to better characterize the genetic landscape of EC in a non-invasive and dynamic manner. Uterine aspirates (UAs) from 60 patients with EC were obtained during surgery and analyzed by next-generation sequencing (NGS). Blood samples, collected at surgery, were used for cell-free DNA (cfDNA) and circulating tumor cell (CTC) analyses. Finally, personalized therapies were tested in patient-derived xenografts (PDXs) generated from the UAs. NGS analyses revealed the presence of genetic alterations in 93% of the tumors. Circulating tumor DNA (ctDNA) was present in 41.2% of cases, mainly in patients with high-risk tumors, thus indicating a clear association with a more aggressive disease. Accordingly, the results obtained during the post-surgery follow-up indicated the presence of ctDNA in three patients with progressive disease. Moreover, 38.9% of patients were positive for CTCs at surgery. Finally, the efficacy of targeted therapies based on the UA-specific mutational landscape was demonstrated in PDX models. Our study indicates the potential clinical applicability of a personalized strategy based on a combination of different liquid biopsies to characterize and monitor tumor evolution, and to identify targeted therapies.
近年来，子宫内膜癌（EC）的发病率和死亡率有所上升，因此需要更精确的管理。为此，我们结合了不同类型的液体活检，以非侵入性和动态的方式更好地表征EC的基因图谱。在手术过程中获取了60例EC患者的子宫吸出物（UA），并通过二代测序（NGS）进行分析。手术时采集的血样用于游离DNA（cfDNA）和循环肿瘤细胞（CTC）分析。最后，在由UA生成的患者来源异种移植瘤（PDX）中测试个性化疗法。NGS分析显示93%的肿瘤存在基因改变。41.2%的病例中存在循环肿瘤DNA（ctDNA），主要见于高危肿瘤患者，这表明其与更具侵袭性的疾病明显相关。相应地，术后随访结果表明，3例疾病进展患者中存在ctDNA。此外，38.9%的患者在手术时CTC呈阳性。最后，在PDX模型中证明了基于UA特异性突变图谱的靶向治疗的疗效。我们的研究表明，基于不同液体活检组合的个性化策略在表征和监测肿瘤进展以及识别靶向治疗方面具有潜在的临床应用价值。
