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小儿肾癌的液体活检:I期和IV期病例比较

Liquid Biopsy in Pediatric Renal Cancer: Stage I and Stage IV Cases Compared.

作者信息

Rossi Elisabetta, Zin Angelica, Facchinetti Antonella, Poggiana Cristina, Tombolan Lucia, Affinita Maria Carmen, Bonvini Paolo, Santoro Luisa, Schiavi Francesca, Bisogno Gianni, Zamarchi Rita

机构信息

Department of Surgery, Oncology and Gastroenterology, Oncology Section, University of Padova, Padua, Italy.

Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.

出版信息

Diagnostics (Basel). 2020 Oct 12;10(10):810. doi: 10.3390/diagnostics10100810.

DOI:10.3390/diagnostics10100810
PMID:33053902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7599903/
Abstract

Pediatric renal cancer is rare, and robust evidence for treatment recommendations is lacking. In the perspective of personalized medicine, clinicians need new biomarkers to improve risk stratification and patients' follow-up. Herein, we analyzed some liquid biopsy tools, which have been never tested in pediatric renal cancer: namely, circulating tumor cells (CTCs); the expression of M30, an apoptosis marker, to test CTC metastatic potential; and c-MET expression in CTCs, because of its role in renal cancer progression and drug-resistance. Furthermore, we evaluated the Circulating Endothelial Cells (CECs), whose utility we previously demonstrated in adult metastatic renal cancer treated with anti-angiogenic therapy. We compared two renal cell carcinomas of clear-cell type, stage I and IV, which underwent surgery and surgery plus Sunitinib, respectively. Baseline CTC level and its changes during follow-up were consistent with patients' outcome. In case 2, stage IV, the analysis of CECs performed during Sunitinib revealed a late response to treatment consistent with poor outcome, as the finding of M30-negative, viable cells. Noteworthily, few CTCs were MET-positive in both cases. Our study highlights the feasibility for a change in the prognostic approach and follow-up of childhood renal cancer, with a view to guide a better treatment design.

摘要

小儿肾癌较为罕见,且缺乏用于治疗建议的确凿证据。从精准医学的角度来看,临床医生需要新的生物标志物来改善风险分层和患者随访。在此,我们分析了一些从未在小儿肾癌中进行过测试的液体活检工具:即循环肿瘤细胞(CTC);凋亡标志物M30的表达,以测试CTC的转移潜能;以及CTC中c-MET的表达,因为其在肾癌进展和耐药性中发挥作用。此外,我们评估了循环内皮细胞(CEC),我们之前已证明其在接受抗血管生成治疗的成人转移性肾癌中的效用。我们比较了两例透明细胞型肾细胞癌,分别为I期和IV期,它们分别接受了手术和手术加舒尼替尼治疗。基线CTC水平及其在随访期间的变化与患者的预后一致。在病例2(IV期)中,在舒尼替尼治疗期间对CEC的分析显示对治疗的晚期反应与不良预后一致,表现为发现M30阴性的存活细胞。值得注意的是,两例中均仅有少数CTC为MET阳性。我们的研究强调了改变儿童肾癌预后方法和随访的可行性,以期指导更好的治疗设计。

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Front Pediatr. 2021 Apr 29;9:652583. doi: 10.3389/fped.2021.652583. eCollection 2021.

本文引用的文献

1
Prognostic Role of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma: A Large, Multicenter, Prospective Trial.循环肿瘤细胞在转移性肾细胞癌中的预后作用:一项大型、多中心、前瞻性试验
Oncologist. 2021 Sep;26(9):740-750. doi: 10.1002/onco.13842. Epub 2021 Jun 17.
2
Biology and treatment of renal tumours in childhood.儿童肾肿瘤的生物学特性与治疗
Eur J Cancer. 2016 Nov;68:179-195. doi: 10.1016/j.ejca.2016.09.005. Epub 2016 Oct 28.
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Development of a Novel c-MET-Based CTC Detection Platform.一种基于新型c-MET的循环肿瘤细胞检测平台的开发。
Mol Cancer Res. 2016 Jun;14(6):539-47. doi: 10.1158/1541-7786.MCR-16-0011. Epub 2016 Mar 7.
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Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.乳头状肾细胞癌的综合分子特征分析
N Engl J Med. 2016 Jan 14;374(2):135-45. doi: 10.1056/NEJMoa1505917. Epub 2015 Nov 4.
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An approach to renal masses in pediatrics.小儿肾脏肿块的处理方法。
Pediatrics. 2015 Jan;135(1):142-58. doi: 10.1542/peds.2014-1011. Epub 2014 Dec 1.
6
Challenges in circulating tumour cell research.循环肿瘤细胞研究中的挑战。
Nat Rev Cancer. 2014 Sep;14(9):623-31. doi: 10.1038/nrc3820. Epub 2014 Jul 31.
7
Renal cell carcinoma in children and adolescence: our experience.儿童及青少年肾细胞癌:我们的经验
Afr J Paediatr Surg. 2014 Apr-Jun;11(2):101-4. doi: 10.4103/0189-6725.132786.
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Children's Oncology Group's 2013 blueprint for research: renal tumors.儿童肿瘤学组 2013 年研究蓝图:肾肿瘤。
Pediatr Blood Cancer. 2013 Jun;60(6):994-1000. doi: 10.1002/pbc.24419. Epub 2012 Dec 19.
9
Dynamic changes of live/apoptotic circulating tumour cells as predictive marker of response to sunitinib in metastatic renal cancer.循环肿瘤细胞活/凋亡的动态变化作为预测转移性肾细胞癌对舒尼替尼反应的标志物。
Br J Cancer. 2012 Oct 9;107(8):1286-94. doi: 10.1038/bjc.2012.388. Epub 2012 Sep 6.
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Phase I and pharmacokinetic study of sunitinib in pediatric patients with refractory solid tumors: a children's oncology group study.舒尼替尼在儿科难治性实体瘤患者中的 I 期和药代动力学研究:一项儿童肿瘤学组研究。
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