Identification of molecular phenotypic descriptors of breast capsular contracture formation using informatics analysis of the whole genome transcriptome.
Breast capsular contracture formation following silicone implant augmentation/reconstruction is a common complication that remains poorly understood. The aim of this study was to identify potential biomarkers implicated in breast capsular contracture formation by using, for the first time, whole genome arrays. Biopsy samples were taken from 18 patients (23 breast capsules) with Baker Grade I-II (Control) and Baker Grade III-IV (Contracted). Whole genome microarrays were performed and six significantly dysregulated genes were selected for further validation with quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Hematoxylin and eosin was also carried out to compare the histological characteristics of control and contracted samples. Microarray results showed that aggrecan, tissue inhibitor of metalloproteinase 4 (TIMP4), and tumor necrosis factor superfamily (ligand) member 11 were significantly down-regulated in contracted capsules; while matrix metallopeptidase 12, serum amyloid A 1, and interleukin 8 (IL8) were significantly up-regulated. The dysregulation of aggrecan, tumor necrosis factor superfamily (ligand) member 11, TIMP4, and IL8 was validated by quantitative reverse transcriptase polymerase chain reaction (p < 0.05). Immunohistochemistry confirmed an increased protein expression for IL8 and matrix metallopeptidase 12 in contracted capsules (p < 0.05), and decreased protein expression of TIMP4 (p < 0.05). This study has shown, for the first time, a number of unique biomarkers of significance in capsular contracture formation. IL8 and TIMP4 may serve as potential key diagnostic, therapeutic, and prognostic biomarkers in capsular contracture formation.
Plastic & Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, United Kingdom.
Daniel J T
DJ
Kyle
Alison G
AG
Harvey
Barbara
B
Shih
Kian T
KT
Tan
Iskander H
IH
Chaudhry
Ardeshir
A
Bayat
D053674:Aggrecans / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018427:Breast Implants / Q000009:adverse effects*; D003286:Contracture / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism*; D016462:Mammaplasty / Q000009:adverse effects*; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D053245:RANK Ligand / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000378:metabolism; D020034:Silicone Gels / Q000009:adverse effects; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D059467:Transcriptome / Q000235:genetics; D015854:Up-Regulation; D000097792:Tissue Inhibitor of Metalloproteinase-4
D053674:Aggrecans; D015415:Biomarkers; D016209:Interleukin-8; D053508:Matrix Metalloproteinase 12; D053245:RANK Ligand; D000685:Serum Amyloid A Protein; D020034:Silicone Gels; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C508319:ACAN protein, human; C521404:SAA1 protein, human; C507122:MMP12 protein, human