A functional gene expression analysis in epithelial sinonasal cancer: Biology and clinical relevance behind three histological subtypes

Loris De Cecco, Mara Serena Serafini, Carla Facco, Roberta Granata, Ester Orlandi, Carlo Fallai, Lisa Licitra, Edoardo Marchesi, Federica Perrone, Silvana Pilotti, Pasquale Quattrone, Cesare Piazza, Fausto Sessa, Mario Turri-Zanoni, Paolo Battaglia, Paolo Castelnuovo, Paolo Antognoni, Silvana Canevari, Paolo Bossi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)94-101
Number of pages8
JournalOral Oncology
Volume90
DOIs
Publication statusPublished - Mar 2019

Fingerprint

Gene Expression
Neoplasms
Squamous Cell Carcinoma
Neoplasm Genes
Discriminant Analysis
Least-Squares Analysis
Cellular Microenvironment
Gene Expression Profiling
Microarray Analysis
Rare Diseases
Keratinocytes
Genes
Ligation
Immune System
Complementary DNA
Neurons

Keywords

  • Cancer biology
  • Gene expression
  • Neuroendocrine signature
  • Sinonasal epithelial cancer
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

Cite this

A functional gene expression analysis in epithelial sinonasal cancer : Biology and clinical relevance behind three histological subtypes. / 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.

In: Oral Oncology, Vol. 90, 03.2019, p. 94-101.

Research output: Contribution to journalArticle

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. / A functional gene expression analysis in epithelial sinonasal cancer : Biology and clinical relevance behind three histological subtypes. In: Oral Oncology. 2019 ; Vol. 90. pp. 94-101.
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abstract = "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.",
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AU - Facco, Carla

AU - Granata, Roberta

AU - Orlandi, Ester

AU - Fallai, Carlo

AU - Licitra, Lisa

AU - Marchesi, Edoardo

AU - Perrone, Federica

AU - Pilotti, Silvana

AU - Quattrone, Pasquale

AU - Piazza, Cesare

AU - Sessa, Fausto

AU - Turri-Zanoni, Mario

AU - Battaglia, Paolo

AU - Castelnuovo, Paolo

AU - Antognoni, Paolo

AU - Canevari, Silvana

AU - Bossi, Paolo

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N2 - 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.

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KW - Neuroendocrine signature

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KW - Tumor microenvironment

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