Vautrot Valentin, Hervieu Alice, Bertaut Aurélie, Charon-Barra Céline, Naiken Isen, Causseret Sylvain, Chaigneau Loic, Desmoulins Isabelle, Rederstoff Emilie, Isambert Nicolas, Gobbo Jessica
Department of Medical Oncology, Early Phase Unit, Georges-François Leclerc Centre, Dijon, France.
Unit of Methodology, Biostatistics and Data Management, Georges-François Leclerc Centre, Dijon, France.
JMIR Res Protoc. 2025 Sep 9;14:e63718. doi: 10.2196/63718.
Sarcomas are rare cancer with a heterogeneous group of tumors. They affect both genders across all age groups and present significant heterogeneity, with more than 70 histological subtypes. Despite tailored treatments, the high metastatic potential of sarcomas remains a major factor in poor patient survival, as metastasis is often the leading cause of death. Currently, metastatic risk assessment relies mainly on histological grading; yet, this method has limitations due to the disease's heterogeneity. Advances in genomic and transcriptomic research have identified potential molecular signatures, but these approaches lack reproducibility and prognostic reliability. Therefore, new biomarkers are essential for improving risk prediction and therapy adaptation. Recent studies highlight that sarcoma cells secrete extracellular vesicles, particularly small extracellular vesicles (sEVs). These nanovesicles, abundant in bodily fluids such as blood, urine, and saliva, play a crucial role in tumor development, growth, and metastasis. sEVs contain proteins and nucleic acids that mirror tumor characteristics. Given their presence in blood, sEVs offer a promising avenue for noninvasive molecular cancer analysis via liquid biopsy. Preliminary studies in Ewing sarcoma have shown substantial alterations in sEV-derived transcripts, underscoring their potential in tracking disease progression and treatment efficacy.
This study aims to investigate whether sEVs can serve as reliable biomarkers for monitoring sarcoma progression and predicting recurrence risk.
This prospective, multicentric pilot study will enroll adult patients diagnosed with localized or metastatic liposarcomas, leiomyosarcomas, or undifferentiated pleomorphic sarcomas at 3 French cancer centers. The study's primary goal is to quantify sEVs and analyze their protein and RNA content in the blood of patients with localized or metastatic sarcomas before and after the treatment. sEVs will be isolated from plasma samples, and protein and microRNA concentration will be determined. Research will last, on average, 6 months for patients with localized sarcoma and 4 months for patients with metastatic sarcoma.
We expect to identify differences in exosome levels based on disease stage and observe correlations between exosome dynamics and treatment response. If confirmed, these findings could establish sEVs as noninvasive biomarkers for monitoring therapy effectiveness and disease progression in patients with sarcoma.
This study could establish a novel, noninvasive biomarker for sarcoma prognosis and treatment monitoring. If successful, a nationwide study will be launched to confirm findings in a larger patient cohort, potentially revolutionizing sarcoma management and improving patient outcomes.
ClinicalTrials.gov NCT03800121; https://clinicaltrials.gov/ct2/show/study/NCT03800121.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/63718.
肉瘤是一种罕见的癌症，肿瘤类型多样。它可发生于所有年龄组的男女，具有显著的异质性，有70多种组织学亚型。尽管有针对性的治疗，但肉瘤的高转移潜能仍是患者生存率低的主要因素，因为转移往往是主要死因。目前，转移风险评估主要依赖组织学分级；然而，由于该疾病的异质性，这种方法存在局限性。基因组和转录组研究的进展已经确定了潜在的分子特征，但这些方法缺乏可重复性和预后可靠性。因此，新的生物标志物对于改善风险预测和治疗适应性至关重要。最近的研究表明，肉瘤细胞会分泌细胞外囊泡，特别是小细胞外囊泡（sEVs）。这些纳米囊泡在血液、尿液和唾液等体液中大量存在，在肿瘤发生、生长和转移中起关键作用。sEVs包含反映肿瘤特征的蛋白质和核酸。鉴于它们存在于血液中，sEVs为通过液体活检进行非侵入性分子癌症分析提供了一条有前景的途径。尤因肉瘤的初步研究表明，sEV衍生转录本有显著改变，凸显了它们在追踪疾病进展和治疗效果方面的潜力。
本研究旨在调查sEVs是否可作为监测肉瘤进展和预测复发风险的可靠生物标志物。
这项前瞻性、多中心的试点研究将纳入在3家法国癌症中心被诊断为局限性或转移性脂肪肉瘤、平滑肌肉瘤或未分化多形性肉瘤的成年患者。该研究的主要目标是量化sEVs，并分析局限性或转移性肉瘤患者治疗前后血液中它们的蛋白质和RNA含量。将从血浆样本中分离sEVs，并测定蛋白质和微小RNA浓度。局限性肉瘤患者的研究平均持续6个月，转移性肉瘤患者的研究平均持续4个月。
我们期望根据疾病阶段确定外泌体水平的差异，并观察外泌体动态与治疗反应之间的相关性。如果得到证实，这些发现可能会将sEVs确立为监测肉瘤患者治疗效果和疾病进展的非侵入性生物标志物。
本研究可为肉瘤预后和治疗监测建立一种新的非侵入性生物标志物。如果成功，将开展一项全国性研究，在更大的患者队列中证实这些发现，这可能会彻底改变肉瘤的管理并改善患者预后。
ClinicalTrials.gov NCT03800121；https://clinicaltrials.gov/ct2/show/study/NCT03800121。
国际注册报告识别码（IRRID）：DERR1-10.2196/63718。
