Genomic Analysis Defines a Cancer-Specific Gene Expression Signature for Human Squamous Cell Carcinoma and Distinguishes Malignant Hyperproliferation.

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Genomic Analysis Defines a Cancer-Specific Gene Expression Signature for Human Squamous Cell Carcinoma and Distinguishes Malignant Hyperproliferation from Benign Hyperplasia Asifa S. Haider, Sara B. Peters, Helen Kaporis, Irma Cardinale, Ji Fei, Jurg Ott, Miki Blumenberg, Ann M. Bowcock, James G. Krueger, John A. Carucci Journal of Investigative Dermatology Volume 126, Issue 4, Pages 869-881 (April 2006) DOI: 10.1038/sj.jid.5700157 Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Gene expression profiling of SCC and psoriasis. Gene array analysis of mRNA from eight squamous cell carcinoma (SCC), eight site-matched non-tumor-bearing (N), eight psoriasis (P), and five non-lesional (NL) skin biopsies: mRNA was hybridized to individual oligonucleotide arrays containing ∼12,000 human genes (HG-U95A/Av2 chips). Heat maps show unsupervised hierarchical clustering for gene expression differences that are statistically significant (P<0.05, after correction for multiplicity). Full tables of gene expression data are given in Tables S1–S5, whereas P-values for all expression differences are given in Table S6. (a) “SCC cluster”: heat map of the 1,048 genes upregulated in SCC versus N (red area) and 870 genes downregulated in SCC versus N (green area). (b) Histological comparison of benign versus malignant hyperproliferative diseases: representative immunohistochemical hematoxylin and eosin staining of P, SCC, NL, and N. (c) “Common cluster”: heat map of 398 genes commonly upregulated in SCC versus N, and P versus NL. (d) “SCC-specific cluster”: heat map of 582 genes upregulated in SCC versus N but not increased in P. (e) Direct comparison of SCC with P: heat map of 2,520 genes up- or downregulated in SCC versus P. Expressions in site-matched (N) skin are not considered. Journal of Investigative Dermatology 2006 126, 869-881DOI: (10.1038/sj.jid.5700157) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Real time RT-PCR confirmation of selected genes differentially expressed in SCC and psoriasis lesions. Mean values of gene expression for selected genes are graphically represented after normalization of expressions using gene to HARP mRNA. mRNA was analyzed from SCC specimens (SCC), site-matched normal (N), psoriasis (P), and non-lesional (NL) skin biopsies (n=7 for each): error bar shown, *P<0.05; **P<0.01; **P<0.001. (a) Genes upregulated in both SCC and psoriasis, SCC>N and P>N: DEFB4, SERPINB3, STAT1, K16, WNT 5A, and CEACAM5. (b) SCC-specific genes, SCC>N and SCC>P: hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) and FZD6. (c) MMPs in SCC and psoriasis: MMP1, MMP10, MMP12, and MMP13. (d) Genes differentially regulated in SCC versus psoriasis, SCC> or <P: genes with increased expression in SCC: cathepsin L2 (CTSL2), STAT3, cystatin E/M (CST6), and MSMB; genes with decreased expression in SCC: iNOS, CD83, CD8a, and GZMB. (e) PTN is downregulated in SCC. Journal of Investigative Dermatology 2006 126, 869-881DOI: (10.1038/sj.jid.5700157) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Immunohistochemical analysis of MMPs and CD8+ and CD83+ cells in SCC and psoriasis. Skin biopsies in non-lesional (NL), psoriasis lesions (LS) and SCC tumor specimens. Representative MMPs (MMP1, 10, and 13) stain strongly in SCC. Equivalent numbers of CD8+ cells were seen in SCC and LS, whereas few CD83+ cells were seen in SCC tumor specimens as compared to NL and LS. Black arrows point to the tumor infiltrates. Original magnification: × 10; bar=100μm. Journal of Investigative Dermatology 2006 126, 869-881DOI: (10.1038/sj.jid.5700157) Copyright © 2006 The Society for Investigative Dermatology, Inc Terms and Conditions