Transcriptional profiling identifies an interferon-associated host immune response in invasive squamous cell carcinoma of the skin
Corresponding Author
Joerg Wenzel
Department of Dermatology, University of Bonn, Bonn, Germany
Fax: +49-228-287-90-6969.
Department of Dermatology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, GermanySearch for more papers by this authorStefan Tomiuk
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorSabine Zahn
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorDaniel Küsters
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorAnja Vahsen
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorAndreas Wiechert
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorSandra Mikus
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorMichael Birth
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorMarina Scheler
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorDagmar von Bubnoff
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorJens M. Baron
Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen, Germany
Search for more papers by this authorHans F. Merk
Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen, Germany
Search for more papers by this authorCornelia Mauch
Department of Dermatology and Venerology and Center for Molecular Medicine, University of Cologne, Cologne, Germany
Search for more papers by this authorThomas Krieg
Department of Dermatology and Venerology and Center for Molecular Medicine, University of Cologne, Cologne, Germany
Search for more papers by this authorThomas Bieber
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorAndreas Bosio
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorKay Hofmann
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorThomas Tüting
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorBettina Peters
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorCorresponding Author
Joerg Wenzel
Department of Dermatology, University of Bonn, Bonn, Germany
Fax: +49-228-287-90-6969.
Department of Dermatology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, GermanySearch for more papers by this authorStefan Tomiuk
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorSabine Zahn
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorDaniel Küsters
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorAnja Vahsen
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorAndreas Wiechert
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorSandra Mikus
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorMichael Birth
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorMarina Scheler
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorDagmar von Bubnoff
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorJens M. Baron
Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen, Germany
Search for more papers by this authorHans F. Merk
Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen, Germany
Search for more papers by this authorCornelia Mauch
Department of Dermatology and Venerology and Center for Molecular Medicine, University of Cologne, Cologne, Germany
Search for more papers by this authorThomas Krieg
Department of Dermatology and Venerology and Center for Molecular Medicine, University of Cologne, Cologne, Germany
Search for more papers by this authorThomas Bieber
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorAndreas Bosio
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorKay Hofmann
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorThomas Tüting
Department of Dermatology, University of Bonn, Bonn, Germany
Search for more papers by this authorBettina Peters
Miltenyi Biotec GmbH, MACSmolecular Business Unit, Cologne, Germany
Search for more papers by this authorAbstract
Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the 2 most common types of nonmelanoma skin cancer. Both derive from keratinocytes but show a distinct biological behavior. Here we present transcriptional profiling data of a large cohort of tumor patients (SCC, n = 42; BCC, n = 114). Differentially expressed genes reflect known features of SCC and BCC including the typical cytokeratin pattern as well as upregulation of characteristic cell proliferation genes. Additionally, we found increased expression of interferon (IFN)-regulated genes (including IFI27, IFI30, Mx1, IRF1 and CXCL9) in SCC, and to a lower extent in BCC. The expression of IFN-regulated genes correlated with the extent of the lesional immune-cell infiltrate. Immunohistological examinations confirmed the expression of IFN-regulated genes in association with a CXCR3+ cytotoxic inflammatory infiltrate on the protein level. Of note, a small subset of SCC samples with low expression of IFN-regulated genes included most organ transplant recipients receiving immunosuppressive medication. Collectively, our findings support the concept that IFN-associated host responses play an important role in tumor immunosurveillance in the skin. © 2008 Wiley-Liss, Inc.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| IJC_23799_sm_suppinfoFigure1.tif1.3 MB | Supplemental figure 1: Unsupervised clustering of selected genes. Genes which were identified to differentiate between SCC and BCC belonged mostly to the gene clusters “Keratin”, “Matrix”, “Cell cycle” and “IFN-signature”. Unsupervised clustering including these genes only was able to distinguish almost all SCC from BCC specimens. Only 4 SCC and 2 BCC probes we incorrectly grouped (given in blue color). The cluster-specificity was 98%, which supports the validity of our approach. |
| IJC_23799_sm_suppinfoFigure2.tif245 KB | Supplemental figure 2: Correlation analyses between the expression rate of the IFN-regulated genes IFI27, IFI30, Mx1 and CXCL9 as detected by PIQOR and the extent of the lesional inflammation seen during histological analyses of the corresponding sample. The figure depicts correlation analyses between the expression rate of selected IFN-regulated genes as detected in PIQOR microarray analyses and the extent of the lesional inflammation. This inflammation was examined by conventional histology and scored semiquantitatively: +++/strong, ++/moderate, +/weak and 0/none. Statistical analyses were performed using SPSS14, given is the Spearman's correlation coefficient rho. |
| IJC_23799_sm_suppinfoFigure3.tif186.4 KB | Supplemental figure 3: Extent of the lesional inflammation in SCC-subgroups. As described above, unsupervised clustering of the SCC samples included in the PIQOR microarray analyses identified two SCC subclusters: one with high expression of IFN-regulated genes (subgroup B, “IFN-high”) and one with low expression (subgroup A, “IFN-low”). As shown in the figure, these groups differed significantly concerning the lesional inflammation seen in the corresponding histological specimens: the extent of the lesional inflammation detected in the “IFN-high” subset A was significantly higher than that in the “IFN-low” subgroup B (p<0.01, Mann-Whitney-U-test). |
| IJC_23799_sm_suppinfoTable1.doc233 KB | Supplemental table1: Gene identified in SAGE analyses (p<0.01 when compared with healthy skin). |
| IJC_23799_sm_suppinfoTable2.doc185 KB | Supplemental table 2: Differentially expressed genes (SCC <-> BCC) as identified in PIQOR-analyses. |
| IJC_23799_sm_suppinfoTable3.doc100.5 KB | Supplemental table 3: Detailed patient data (SCC patients). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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