Gene Expression Profiling of Olfactory Neuroblastoma Helps Identify Prognostic Pathways and Define Potentially Therapeutic Targets
Chiara Romani, Eliana Bignotti, Davide Mattavelli, Anna Bozzola, Luigi Lorini, Michele Tomasoni, Laura Ardighieri, Vittorio Rampinelli, Alberto Paderno, Simonetta Battocchio, Cristina Gurizzan, Paolo Castelnuovo, Mario Turri‐Zanoni, Carla Facco, Fausto Sessa, Alberto Schreiber, Marco Ferrari, Antonella Ravaggi, Alberto Deganello, Piero Nicolai, Michela Buglione, Davide Tomasini, Roberto Maroldi, Cesare Piazza, Stefano Calza, Paolo Bossi
Abstract
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.