title: Differential expression of degradome components in cutaneous squamous cell carcinomas.
abstract: Although the cure rate for cutaneous squamous cell carcinoma is high, the diverse spectrum of squamous cell carcinoma has made it difficult for early diagnosis, particularly the aggressive tumors that are highly associated with mortality. Therefore, molecular markers are needed as an adjunct to current staging methods for diagnosing high-risk lesions, and stratifying those patients with aggressive tumors. To identify such biomarkers, we have examined a comprehensive set of 200 histologically defined squamous cell carcinoma and normal skin samples by using a combination of microarray, QRT-PCR and immunohistochemistry analyses. A characteristic and distinguishable profile including matrix metalloproteinase (MMP) as well as other degradome components was differentially expressed in squamous cell carcinoma compared with normal skin samples. The expression levels of some of these genes including matrix metallopeptidase 1 (MMP1), matrix metallopeptidase 10 (MMP10), parathyroid hormone-like hormone (PTHLH), cyclin-dependent kinase inhibitor 2A (CDKN2A), A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), FBJ osteosarcoma oncogene (FOS), interleukin 6 (IL6) and reversion-inducing-cysteine-rich protein with kazal motifs (RECK) were significantly differentially expressed (P≤0.02) in squamous cell carcinoma compared with normal skin. Furthermore, based on receiver operating characteristic analyses, the mRNA and protein levels of MMP1 are significantly higher in aggressive tumors compared with non-aggressive tumors. Given that MMPs represent the most prominent family of proteinases associated with tumorigenesis, we believe that they may have an important role in modulating the tumor microenvironment of squamous cell carcinoma.
authors.affiliation: Department of Plastic and Reconstructive Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Nijaguna B
authors.initials: NB
authors.lastname: Prasad
authors.affiliation: Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Fischer
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Alice Y
authors.initials: AY
authors.lastname: Chuang
authors.affiliation: Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Wright
authors.affiliation: Department of Biostatistics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Biostatistics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hua-Ling
authors.initials: HL
authors.lastname: Tsai
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.affiliation: Department of Dermatology, University of Maryland, Baltimore, MD, USA.
authors.forename: Nanette J
authors.initials: NJ
authors.lastname: Liegeois
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Allan D
authors.initials: AD
authors.lastname: Hess
authors.affiliation: 1] Department of Plastic and Reconstructive Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA [2] Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Tufaro
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor