IL-10 and integrin signaling pathways are associated with head and neck cancer progression

Sophia Bornstein, Mark Schmidt, Gabrielle Choonoo, Trevor Levin, Joe Gray, Charles Thomas, Melissa Wong, Shannon McWeeney

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Head and neck cancer is morbid with a poor prognosis that has not significantly improved in the past several decades. The purpose of this study was to identify biological pathways underlying progressive head and neck cancer to inform prognostic and adjuvant strategies. We identified 235 head and neck cancer patients in The Cancer Genome Atlas (TCGA) with sufficient clinical annotation regarding therapeutic treatment and disease progression to identify progressors and non-progressors. We compared primary tumor gene expression and mutational status between these two groups. Results: 105 genes were differentially expressed between progressors and nonprogressors (FDR <0.05). Pathway analyses revealed deregulation (FDR <0.05) of multiple pathways related to integrin signaling as well as IL-10 signaling. A number of genes were uniquely mutated in the progressor cohort including increased frequency of truncating mutations in CTCF (P = 0.007). An 11-gene signature derived from a combination of unique mutations and differential expression was identified (PAGE4, SMTNL1, VTN, CA5A, C1orf43, KRTAP19-1, LEP, HRH4, PAGE5, SEZ6L, CREB3). This signature was associated with decreased overall survival (Logrank Test; P = 0.03443). Cox modeling of both key clinical features and the signature was significant (P = 0.032) with the greatest prognostic improvement seen in the model based on nodal extracapsular spread and alcohol use alone (P = 0.004). Conclusions: Molecular analyses of head and neck cancer tumors that progressed despite treatment, identified IL-10 and integrin pathways to be strongly associated with cancer progression. In addition, we identified an 11-gene signature with implications for patient prognostication. Mutational analysis highlighted a potential role for CTCF, a crucial regulator of long-range chromatin interactions, in head and neck cancer progression.

Original languageEnglish (US)
Article number38
JournalBMC Genomics
Volume17
Issue number1
DOIs
StatePublished - Jan 8 2016

Fingerprint

Head and Neck Neoplasms
Integrins
Interleukin-10
Genes
Neoplasms
Atlases
Mutation Rate
Chromatin
Disease Progression
Therapeutics
Alcohols
Genome
Gene Expression
Mutation
Survival

Keywords

  • CTCF
  • Head and neck cancer
  • HNSCC
  • IL-10
  • Integrin
  • Mutation
  • RNA-seq
  • Signature
  • TCGA

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

IL-10 and integrin signaling pathways are associated with head and neck cancer progression. / Bornstein, Sophia; Schmidt, Mark; Choonoo, Gabrielle; Levin, Trevor; Gray, Joe; Thomas, Charles; Wong, Melissa; McWeeney, Shannon.

In: BMC Genomics, Vol. 17, No. 1, 38, 08.01.2016.

Research output: Contribution to journalArticle

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abstract = "Background: Head and neck cancer is morbid with a poor prognosis that has not significantly improved in the past several decades. The purpose of this study was to identify biological pathways underlying progressive head and neck cancer to inform prognostic and adjuvant strategies. We identified 235 head and neck cancer patients in The Cancer Genome Atlas (TCGA) with sufficient clinical annotation regarding therapeutic treatment and disease progression to identify progressors and non-progressors. We compared primary tumor gene expression and mutational status between these two groups. Results: 105 genes were differentially expressed between progressors and nonprogressors (FDR <0.05). Pathway analyses revealed deregulation (FDR <0.05) of multiple pathways related to integrin signaling as well as IL-10 signaling. A number of genes were uniquely mutated in the progressor cohort including increased frequency of truncating mutations in CTCF (P = 0.007). An 11-gene signature derived from a combination of unique mutations and differential expression was identified (PAGE4, SMTNL1, VTN, CA5A, C1orf43, KRTAP19-1, LEP, HRH4, PAGE5, SEZ6L, CREB3). This signature was associated with decreased overall survival (Logrank Test; P = 0.03443). Cox modeling of both key clinical features and the signature was significant (P = 0.032) with the greatest prognostic improvement seen in the model based on nodal extracapsular spread and alcohol use alone (P = 0.004). Conclusions: Molecular analyses of head and neck cancer tumors that progressed despite treatment, identified IL-10 and integrin pathways to be strongly associated with cancer progression. In addition, we identified an 11-gene signature with implications for patient prognostication. Mutational analysis highlighted a potential role for CTCF, a crucial regulator of long-range chromatin interactions, in head and neck cancer progression.",
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AU - Wong, Melissa

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