Dataset Information

Gene Expression Profiling of Olfactory Neuroblastoma Helps Identify Prognostic Pathways and Define Potentially Therapeutic Targets.

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.

SUBMITTER: Romani C

PROVIDER: S-EPMC8196700 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Gene Expression Profiling of Olfactory Neuroblastoma Helps Identify Prognostic Pathways and Define Potentially Therapeutic Targets.

Romani Chiara C Bignotti Eliana E Mattavelli Davide D Bozzola Anna A Lorini Luigi L Tomasoni Michele M Ardighieri Laura L Rampinelli Vittorio V Paderno Alberto A Battocchio Simonetta S Gurizzan Cristina C Castelnuovo Paolo P Turri-Zanoni Mario M Facco Carla C Sessa Fausto F Schreiber Alberto A Ferrari Marco M Ravaggi Antonella A Deganello Alberto A Nicolai Piero P Buglione Michela M Tomasini Davide D Maroldi Roberto R Piazza Cesare C Calza Stefano S Bossi Paolo P

Cancers 20210521 11

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 ...[more]

PMID: 34064009

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Project description:BackgroundOlfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory mucosa. The paucity of genomic data has prevented the development of individualized ONB treatments. Here, we investigated the genomic and immune landscape of ONB in Chinese patients.MethodsWhole exome sequencing (WES) and multiplex immunofluorescence (MIF) analysis were performed on tissue samples from 19 Chinese ONB patients. Patients were divided into low- and high-grade groups.ResultsOverall, 929 nonsynonymous alterations were identified in 18 (94.74%) ONB cases. The most prevalent altered cancer-related genes were CTNNB1 (16%) and ZNRF3 (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one case expressed PD-L1 (> 1%) in the tumor region. The percentage of CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor region ranged from 0.03% to 84.9%, with a median of 1.08%. No significant differences were observed between the low- and high-grade groups for clinicopathological features, mutant genes, mutant pathways, TMB, tumor neoantigen burden (TNB), mutant-allele tumor heterogeneity (MATH), PD-L1 expression levels, or CD8+ TIL percentage. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. Notably, CD68+CD163- macrophages accounted for an average of 80.5% of CD68+ macrophages.ConclusionThis study presents data on the genomic and immune landscape of ONB cases in China. CTNNB1 and ZNRF3 were the most prevalent altered cancer-related genes. The results of TMB, PD-L1, and CD8+ Tils suggest that ONB may be insensitive to immunotherapy. M1 macrophages may be positively associated with the prognosis of ONB.Implications for practiceIn this study, the most prevalent altered cancer-related genes were CTNNB1 (16%) and ZNRF3 (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one (1/15) case expressed PD-L1 (> 1%) in the tumor region. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. The higher level of CD68-related macrophages indicates that M1 macrophages potentially play an important role in ONB development that is possibly associated with prognosis.

Dataset Information

Gene Expression Profiling of Olfactory Neuroblastoma Helps Identify Prognostic Pathways and Define Potentially Therapeutic Targets.

Publications

Gene Expression Profiling of Olfactory Neuroblastoma Helps Identify Prognostic Pathways and Define Potentially Therapeutic Targets.

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