Romani Chiara, Bignotti Eliana, Mattavelli Davide, Bozzola Anna, Lorini Luigi, Tomasoni Michele, Ardighieri Laura, Rampinelli Vittorio, Paderno Alberto, Battocchio Simonetta, Gurizzan Cristina, Castelnuovo Paolo, Turri-Zanoni Mario, Facco Carla, Sessa Fausto, Schreiber Alberto, Ferrari Marco, Ravaggi Antonella, Deganello Alberto, Nicolai Piero, Buglione Michela, Tomasini Davide, Maroldi Roberto, Piazza Cesare, Calza Stefano, Bossi Paolo
Angelo Nocivelli Institute of Molecular Medicine, ASST Spedali Civili di Brescia, University of Brescia, 25123 Brescia, Italy.
Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, Italy.
Cancers (Basel). 2021 May 21;13(11):2527. doi: 10.3390/cancers13112527.
Olfactory neuroblastoma (ONB) is a rare sinonasal neoplasm with a peculiar behavior, for which limited prognostic factors are available. Herein, we investigate the transcriptional pathways altered in ONB and correlate them with pathological features and clinical outcomes. We analyze 32 ONB patients treated with curative intent at two independent institutions from 2001 to 2019 for whom there is available pathologic and clinical data. We perform gene expression profiling on primary ONB samples and carry out functional enrichment analysis to investigate the key pathways associated with disease-free survival (DFS). The median age is 53.5 years; all patients undergo surgery and a pure endoscopic approach is adopted in the majority of cases (81.2%). Most patients have advanced disease (stages III-IV, 81.2%) and 84.4% undergo adjuvant (chemo)radiotherapy. The median follow-up is 35 months; 11 (26.8%) patients relapse. Clinical characteristics (gender, stage and Hyams' grade) are not associated with the outcomes. In contrast, TGF-beta binding, EMT, IFN-alpha response, angiogenesis, IL2-STAT5 and IL6-JAK-STAT3 signaling pathways are enriched in patients experiencing recurrence, and significantly associated with shorter DFS. Clustering of transcriptional profiles according to pathological features indicates two distinct molecular groups, defined by either cytokeratin-positive or -negative immunostaining. Definition of the characterizing ONB transcriptomic pathways may pave the way towards tailored treatment approaches.
嗅神经母细胞瘤（ONB）是一种罕见的鼻窦肿瘤，具有独特的生物学行为，目前可用的预后因素有限。在此，我们研究了ONB中改变的转录途径，并将它们与病理特征和临床结果相关联。我们分析了2001年至2019年在两个独立机构接受根治性治疗的32例ONB患者，这些患者有可用的病理和临床数据。我们对原发性ONB样本进行基因表达谱分析，并进行功能富集分析，以研究与无病生存期（DFS）相关的关键途径。中位年龄为53.5岁；所有患者均接受手术，大多数病例（81.2%）采用单纯内镜手术。大多数患者患有晚期疾病（III-IV期，81.2%），84.4%的患者接受辅助（化疗）放疗。中位随访时间为35个月；11例（26.8%）患者复发。临床特征（性别、分期和海姆斯分级）与预后无关。相比之下，TGF-β结合、上皮-间质转化（EMT）、IFN-α反应、血管生成、IL2-STAT5和IL6-JAK-STAT3信号通路在复发患者中富集，并与较短的DFS显著相关。根据病理特征对转录谱进行聚类分析，发现两个不同的分子组，由细胞角蛋白阳性或阴性免疫染色定义。确定ONB的特征性转录组途径可能为量身定制的治疗方法铺平道路。
