Differentiation-promoting culture of competent and noncompetent keratinocytes identifies biomarkers for head and neck cancer

R. Ceder, Y. Haig, M. Merne, A. Hansson, X. Zheng, K. Roberg, Matthias Nees, Kristiina Iljin, B.K. Bloor, P.R. Morgan, B. Fadeel, Roland Grafström (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

17 Citations (Scopus)

Abstract

Aberrant contact-inhibited proliferation and differentiation induction couple with tumor severity, albeit with an imprecise association with prognosis. Assessment of contact inhibition and differentiation-promoting culture in this study of normal and immortalized oral keratinocytes (NOK and SVpgC2a, respectively) demonstrated elevated cloning ability and saturation density in the immortalized versus normal state, including consistent absence of differentiated morphological features. Transcriptomic analysis implicated 48 gene ontology categories, 8 molecular networks, and 10 key regulator genes in confluency-induced differentiation of NOK, all of which remained nonregulated in SVpgC2a. The SVpgC2a versus NOK transcriptome enriched 52 gene ontology categories altogether, 18 molecular networks, and 39 key regulator genes, several of which were associated with epithelial-mesenchymal transition. Assessment of the previously described gene sets relative to training data sets of head and neck squamous cell carcinoma samples, one including data on tumor differentiation and patient outcome and one present in the Human Gene Expression Map, identified four genes with association to poor survival (COX7A1, MFAP5, MPDU1, and POLD1). This gene set predicted poor outcome in an independent data set of 71 head and neck squamous cell carcinomas. The present study defines, for the first time to our knowledge, the broad gene spectrum that couples to induction, and loss, of oral keratinocyte differentiation. Bioinformatics assessments of the results relative to clinical data generated novel differentiation-related tumor biomarkers relevant to patient outcome.

Original languageEnglish
Pages (from-to)457-472
Number of pages16
JournalAmerican Journal of Pathology
Volume180
Issue number2
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

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Head and Neck Neoplasms
Keratinocytes
Biomarkers
Gene Ontology
Regulator Genes
Genes
Contact Inhibition
Epithelial-Mesenchymal Transition
Tumor Biomarkers
Computational Biology
Transcriptome
Organism Cloning
Neoplasms
Gene Expression
Survival
Carcinoma, squamous cell of head and neck
Datasets

Cite this

Ceder, R. ; Haig, Y. ; Merne, M. ; Hansson, A. ; Zheng, X. ; Roberg, K. ; Nees, Matthias ; Iljin, Kristiina ; Bloor, B.K. ; Morgan, P.R. ; Fadeel, B. ; Grafström, Roland. / Differentiation-promoting culture of competent and noncompetent keratinocytes identifies biomarkers for head and neck cancer. In: American Journal of Pathology. 2012 ; Vol. 180, No. 2. pp. 457-472.
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abstract = "Aberrant contact-inhibited proliferation and differentiation induction couple with tumor severity, albeit with an imprecise association with prognosis. Assessment of contact inhibition and differentiation-promoting culture in this study of normal and immortalized oral keratinocytes (NOK and SVpgC2a, respectively) demonstrated elevated cloning ability and saturation density in the immortalized versus normal state, including consistent absence of differentiated morphological features. Transcriptomic analysis implicated 48 gene ontology categories, 8 molecular networks, and 10 key regulator genes in confluency-induced differentiation of NOK, all of which remained nonregulated in SVpgC2a. The SVpgC2a versus NOK transcriptome enriched 52 gene ontology categories altogether, 18 molecular networks, and 39 key regulator genes, several of which were associated with epithelial-mesenchymal transition. Assessment of the previously described gene sets relative to training data sets of head and neck squamous cell carcinoma samples, one including data on tumor differentiation and patient outcome and one present in the Human Gene Expression Map, identified four genes with association to poor survival (COX7A1, MFAP5, MPDU1, and POLD1). This gene set predicted poor outcome in an independent data set of 71 head and neck squamous cell carcinomas. The present study defines, for the first time to our knowledge, the broad gene spectrum that couples to induction, and loss, of oral keratinocyte differentiation. Bioinformatics assessments of the results relative to clinical data generated novel differentiation-related tumor biomarkers relevant to patient outcome.",
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Ceder, R, Haig, Y, Merne, M, Hansson, A, Zheng, X, Roberg, K, Nees, M, Iljin, K, Bloor, BK, Morgan, PR, Fadeel, B & Grafström, R 2012, 'Differentiation-promoting culture of competent and noncompetent keratinocytes identifies biomarkers for head and neck cancer', American Journal of Pathology, vol. 180, no. 2, pp. 457-472. https://doi.org/10.1016/j.ajpath.2011.10.016

Differentiation-promoting culture of competent and noncompetent keratinocytes identifies biomarkers for head and neck cancer. / Ceder, R.; Haig, Y.; Merne, M.; Hansson, A.; Zheng, X.; Roberg, K.; Nees, Matthias; Iljin, Kristiina; Bloor, B.K.; Morgan, P.R.; Fadeel, B.; Grafström, Roland (Corresponding Author).

In: American Journal of Pathology, Vol. 180, No. 2, 2012, p. 457-472.

Research output: Contribution to journalArticleScientificpeer-review

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AU - Ceder, R.

AU - Haig, Y.

AU - Merne, M.

AU - Hansson, A.

AU - Zheng, X.

AU - Roberg, K.

AU - Nees, Matthias

AU - Iljin, Kristiina

AU - Bloor, B.K.

AU - Morgan, P.R.

AU - Fadeel, B.

AU - Grafström, Roland

PY - 2012

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N2 - Aberrant contact-inhibited proliferation and differentiation induction couple with tumor severity, albeit with an imprecise association with prognosis. Assessment of contact inhibition and differentiation-promoting culture in this study of normal and immortalized oral keratinocytes (NOK and SVpgC2a, respectively) demonstrated elevated cloning ability and saturation density in the immortalized versus normal state, including consistent absence of differentiated morphological features. Transcriptomic analysis implicated 48 gene ontology categories, 8 molecular networks, and 10 key regulator genes in confluency-induced differentiation of NOK, all of which remained nonregulated in SVpgC2a. The SVpgC2a versus NOK transcriptome enriched 52 gene ontology categories altogether, 18 molecular networks, and 39 key regulator genes, several of which were associated with epithelial-mesenchymal transition. Assessment of the previously described gene sets relative to training data sets of head and neck squamous cell carcinoma samples, one including data on tumor differentiation and patient outcome and one present in the Human Gene Expression Map, identified four genes with association to poor survival (COX7A1, MFAP5, MPDU1, and POLD1). This gene set predicted poor outcome in an independent data set of 71 head and neck squamous cell carcinomas. The present study defines, for the first time to our knowledge, the broad gene spectrum that couples to induction, and loss, of oral keratinocyte differentiation. Bioinformatics assessments of the results relative to clinical data generated novel differentiation-related tumor biomarkers relevant to patient outcome.

AB - Aberrant contact-inhibited proliferation and differentiation induction couple with tumor severity, albeit with an imprecise association with prognosis. Assessment of contact inhibition and differentiation-promoting culture in this study of normal and immortalized oral keratinocytes (NOK and SVpgC2a, respectively) demonstrated elevated cloning ability and saturation density in the immortalized versus normal state, including consistent absence of differentiated morphological features. Transcriptomic analysis implicated 48 gene ontology categories, 8 molecular networks, and 10 key regulator genes in confluency-induced differentiation of NOK, all of which remained nonregulated in SVpgC2a. The SVpgC2a versus NOK transcriptome enriched 52 gene ontology categories altogether, 18 molecular networks, and 39 key regulator genes, several of which were associated with epithelial-mesenchymal transition. Assessment of the previously described gene sets relative to training data sets of head and neck squamous cell carcinoma samples, one including data on tumor differentiation and patient outcome and one present in the Human Gene Expression Map, identified four genes with association to poor survival (COX7A1, MFAP5, MPDU1, and POLD1). This gene set predicted poor outcome in an independent data set of 71 head and neck squamous cell carcinomas. The present study defines, for the first time to our knowledge, the broad gene spectrum that couples to induction, and loss, of oral keratinocyte differentiation. Bioinformatics assessments of the results relative to clinical data generated novel differentiation-related tumor biomarkers relevant to patient outcome.

U2 - 10.1016/j.ajpath.2011.10.016

DO - 10.1016/j.ajpath.2011.10.016

M3 - Article

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JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

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