Differential expression of degradome components in cutaneous squamous cell carcinomas

Nijaguna B. Prasad, Anne C. Fischer, Alice Y. Chuang, Jerry M. Wright, Ting Yang, Hua Ling Tsai, William H. Westra, Nanette J. Liegeois, Allan D. Hess, Anthony P. Tufaro

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)945-957
Number of pages13
JournalModern Pathology
Volume27
Issue number7
DOIs
StatePublished - 2014

Fingerprint

Squamous Cell Carcinoma
Skin
Metalloproteases
Matrix Metalloproteinases
Neoplasms
Cyclin-Dependent Kinase Inhibitor p16
Thrombospondin 1
Disintegrins
Tumor Microenvironment
Osteosarcoma
Parathyroid Hormone
Oncogenes
ROC Curve
Cysteine
Early Diagnosis
Interleukin-6
Carcinogenesis
Proteins
Peptide Hydrolases
Biomarkers

Keywords

  • cutaneous squamous cell carcinoma
  • degradome
  • gene expression

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Prasad, N. B., Fischer, A. C., Chuang, A. Y., Wright, J. M., Yang, T., Tsai, H. L., ... Tufaro, A. P. (2014). Differential expression of degradome components in cutaneous squamous cell carcinomas. Modern Pathology, 27(7), 945-957. https://doi.org/10.1038/modpathol.2013.217

Differential expression of degradome components in cutaneous squamous cell carcinomas. / Prasad, Nijaguna B.; Fischer, Anne C.; Chuang, Alice Y.; Wright, Jerry M.; Yang, Ting; Tsai, Hua Ling; Westra, William H.; Liegeois, Nanette J.; Hess, Allan D.; Tufaro, Anthony P.

In: Modern Pathology, Vol. 27, No. 7, 2014, p. 945-957.

Research output: Contribution to journalArticle

Prasad, NB, Fischer, AC, Chuang, AY, Wright, JM, Yang, T, Tsai, HL, Westra, WH, Liegeois, NJ, Hess, AD & Tufaro, AP 2014, 'Differential expression of degradome components in cutaneous squamous cell carcinomas', Modern Pathology, vol. 27, no. 7, pp. 945-957. https://doi.org/10.1038/modpathol.2013.217
Prasad, Nijaguna B. ; Fischer, Anne C. ; Chuang, Alice Y. ; Wright, Jerry M. ; Yang, Ting ; Tsai, Hua Ling ; Westra, William H. ; Liegeois, Nanette J. ; Hess, Allan D. ; Tufaro, Anthony P. / Differential expression of degradome components in cutaneous squamous cell carcinomas. In: Modern Pathology. 2014 ; Vol. 27, No. 7. pp. 945-957.
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