Iannó Maria F, Biassoni Veronica, Schiavello Elisabetta, Carenzo Andrea, Boschetti Luna, Gandola Lorenza, Diletto Barbara, Marchesi Edoardo, Vegetti Claudia, Molla Alessandra, Kramm Christof M, van Vuurden Dannis G, Gasparini Patrizia, Gianno Francesca, Giangaspero Felice, Modena Piergiorgio, Bison Brigitte, Anichini Andrea, Vennarini Sabina, Pignoli Emanuele, Massimino Maura, De Cecco Loris
Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy.
Pediatric Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Via Venezian 1, 20133 Milan, Italy.
Cancers (Basel). 2022 Sep 2;14(17):4307. doi: 10.3390/cancers14174307.
Diffuse midline gliomas (DMGs) originate in the thalamus, brainstem, cerebellum and spine. This entity includes tumors that infiltrate the pons, called diffuse intrinsic pontine gliomas (DIPGs), with a rapid onset and devastating neurological symptoms. Since surgical removal in DIPGs is not feasible, the purpose of this study was to profile circulating miRNA expression in DIPG patients in an effort to identify a non-invasive prognostic signature with clinical impact. Using a high-throughput platform, miRNA expression was profiled in serum samples collected at the time of MRI diagnosis and prior to radiation and/or systemic therapy from 47 patients enrolled in clinical studies, combining nimotuzumab and vinorelbine with concomitant radiation. With progression-free survival as the primary endpoint, a semi-supervised learning approach was used to identify a signature that was also tested taking overall survival as the clinical endpoint. A signature comprising 13 circulating miRNAs was identified in the training set ( = 23) as being able to stratify patients by risk of disease progression (log-rank = 0.00014; HR = 7.99, 95% CI 2.38-26.87). When challenged in a separate validation set ( = 24), it confirmed its ability to predict progression (log-rank = 0.00026; HR = 5.51, 95% CI 2.03-14.9). The value of our signature was also confirmed when overall survival was considered (log-rank = 0.0021, HR = 4.12, 95% CI 1.57-10.8). We have identified and validated a prognostic marker based on the expression of 13 circulating miRNAs that can shed light on a patient's risk of progression. This is the first demonstration of the usefulness of nucleic acids circulating in the blood as powerful, easy-to-assay molecular markers of disease status in DIPG. This study provides Class II evidence that a signature based on 13 circulating miRNAs is associated with the risk of disease progression.
弥漫性中线胶质瘤（DMG）起源于丘脑、脑干、小脑和脊柱。该实体包括浸润脑桥的肿瘤，称为弥漫性脑桥内在型胶质瘤（DIPG），其起病迅速且伴有严重的神经症状。由于DIPG无法通过手术切除，本研究的目的是分析DIPG患者循环miRNA的表达情况，以努力确定具有临床意义的非侵入性预后特征。使用高通量平台，对47例参加临床研究的患者在MRI诊断时以及放疗和/或全身治疗前采集的血清样本中的miRNA表达进行了分析，这些患者接受了尼妥珠单抗和长春瑞滨联合同步放疗。以无进展生存期为主要终点，采用半监督学习方法确定一个特征，并以总生存期为临床终点进行了测试。在训练集（n = 23）中确定了一个由13种循环miRNA组成的特征，该特征能够根据疾病进展风险对患者进行分层（对数秩检验P = 0.00014；风险比HR = 7.99，95%置信区间CI 2.38 - 26.87）。在单独的验证集（n = 24）中进行验证时，证实了其预测进展的能力（对数秩检验P = 0.00026；HR = 5.51，95% CI 2.03 - 14.9）。当考虑总生存期时，该特征的价值也得到了证实（对数秩检验P = 0.0021，HR = 4.12，95% CI 1.57 - 10.8）。我们已经确定并验证了一种基于13种循环miRNA表达的预后标志物，该标志物可以揭示患者的进展风险。这是首次证明血液中循环的核酸作为DIPG疾病状态的强大且易于检测的分子标志物的有用性。本研究提供了二级证据，表明基于13种循环miRNA的特征与疾病进展风险相关。
