Identification of biomarkers in Dupuytren's disease by comparative analysis of fibroblasts versus tissue biopsies in disease-specific phenotypes.

阅读量：

作者：

B Shih，D Wijeratne，DJ Armstrong，T Lindau，P Day，A Bayat

展开

摘要：

Biomarkers are molecular mediators that can serve as indicators of normal biological processes, pathologic processes, and therapeutic interventions. This study aims to identify potential biomarkers in Dupuytren's disease (DD), a fibroproliferative benign tumor with an unknown etiology and high recurrence after surgery. Bioinformatic analytical techniques were employed to identify candidate genes that may be differentially expressed in DD, which included gene expression analysis of microarray data and thorough literature searches in genetic linkage and other related biomolecular studies. All DD cases were males with advanced DD (n = 5, 66 years ± 14). RNA was extracted from biopsies and corresponding cultures of normal fascia (unaffected transverse palmar fascia), palmar nodule and cord from each patient. Real-time reverse transcription–polymerase chain reactions were performed to determine the gene expression levels for disease-related transcripts. The bioinformatic analysis revealed 25 candidate genes, which were further short-listed to 6 genes via functional annotation. The 6 selected candidate genes included: A disintegrin and metalloproteinase domain (ADAM12), aldehyde dehydrogenase 1 family member (ALDH1) A1, Iroquois homeobox protein 6 (IRX6), proteoglycan 4 (PRG4), tenascin C (TNC), and periostin (POSTN). The culturing treatments were shown to have significant impact on the gene expression for ALDH1A1, PRG4, and TNC. In tissue biopsies, significant fold changes were observed for ADAM12, POSTN, and TNC in the cord and/or nodule when compared with that of normal fascia. ADAM12 and POSTN are associated with accelerated or abnormal cell growth, whereas TNC has been associated with fibrotic diseases and cell migration. This study demonstrated differential gene expression results in DD tissue biopsies compared with that of their corresponding cultures. ADAM12, POSTN, and TNC were identified from the cord and nodule biopsy samples as potential biomarkers in relation to DD development.

展开

关键词：

Biomarkers Dupuytren's contracture Dupuytren's disease Dupuytren's tissue and fibroblasts culture RT-qPCR

DOI：

10.1016/j.jhsa.2008.09.017

被引量：

年份：

2009