A functional gene expression analysis in epithelial sinonasal cancer: Biology and clinical relevance behind three histological subtypes
Autor: | De Cecco, Loris, Serafini, Mara Serena, Facco, Carla, Granata, Roberta, Orlandi, Ester, Fallai, Carlo, Licitra, Lisa, Marchesi, Edoardo, Perrone, Federica, Pilotti, Silvana, Quattrone, Pasquale, Piazza, Cesare, Sessa, Fausto, Turri-Zanoni, Mario, Battaglia, Paolo, Castelnuovo, Paolo, Antognoni, Paolo, Canevari, Silvana, Bossi, Paolo, TURRI ZANONI, Mario |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
Male
Cancer Research Cell 0302 clinical medicine 80 and over Tumor Microenvironment 030223 otorhinolaryngology Aged 80 and over Tumor Effector Middle Aged Prognosis medicine.anatomical_structure Neuroendocrine Oncology 030220 oncology & carcinogenesis Carcinoma Squamous Cell Female Oral Surgery Adult Cell type Adolescent Maxillary Sinus Neoplasms Cancer biology Biology Gene expression Neuroendocrine signature Sinonasal epithelial cancer Tumor microenvironment 03 medical and health sciences Young Adult Rare Diseases medicine Biomarkers Tumor Humans Clinical significance Gene Aged Retrospective Studies Microarray analysis techniques Gene Expression Profiling Carcinoma Carcinoma Neuroendocrine Transcriptome Gene expression profiling Squamous Cell Cancer research CD8 Biomarkers |
Popis: | Epithelial sinonasal cancers (SNCs) are rare diseases with overlapping morphological features and a dismal prognosis. We aimed to investigate the expression differences among the histological subtypes for discerning their molecular characteristics. We selected 47 SNCs: (i) 21 nonkeratinizing squamous cell carcinomas (NKSCCs), (ii) 13 sinonasal neuroendocrine cancers (SNECs), and (iii) 13 sinonasal undifferentiated cancers (SNUCs). Gene expression profiling was performed by DASL (cDNA-mediated annealing, selection, extension, and ligation) microarray analysis with internal validation by quantitative RT-PCR (RT-qPCR). Relevant molecular patterns were uncovered by sparse partial-least squares discriminant analysis (sPLS-DA), microenvironment cell type (xCell), CIBERSORT, and gene set enrichment (GSEA) analyses. The first two sPLS-DA components stratified samples by histological subtypes. xCell highlighted increased expression of immune components (CD8+ effector memory cells, in SNUC) and "other cells": keratinocytes and neurons in NKSCC and SNEC, respectively. Pathway enrichment was observed in NKSCC (six gene sets, proliferation related), SNEC (one gene set, pancreatic β-cells), and SNUC (twenty gene sets, some of them immune-system related). Major neuroendocrine involvement was observed in all the SNEC samples. Our high-throughput analysis revealed a good diagnostic ability to differentiate NKSCC, SNEC, and SNUC, but indicated that the neuroendocrine pathway, typical and pathognomonic of SNEC is also present at lower expression levels in the other two histological subtypes. The different and specific profiles may be exploited for elucidating their biology and could help to identify prognostic and therapeutic opportunities. |
Databáze: | OpenAIRE |
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