Incisional hernia recurrence through genomic profiling: a pilot study.
OBJECTIVE
Although situational risk factors for incisional hernia formation are known, the methods used to determine who would be most susceptible to develop one are unreliable. We hypothesized that patients with recurrent incisional hernias may possess unique gene expression profiles.


METHODS
Skin and intact fascia were collected from 15 normal control (NC) patients with no hernia history and 18 patients presenting for recurrent incisional hernia (RH) repair. Microarray analysis was performed using whole genome microarray chips on NC (n = 8) and RH (n = 9). These samples were further investigated using a pathway-specific PCR array containing fibrosis-related genes.


RESULTS
Microarray data revealed distinct differences in the gene expression profiles between RH and NC patients. One hundred and sixty-seven genes in the skin and 7 genes in the fascia were differentially expressed, including 8 directly involved in collagen synthesis. In particular, GREMLIN1, or bone morphogenetic protein antagonist 1, was under expressed in skin (fold = 0.49, p < 10(-7), q = 0.0009) and fascia (fold = 0.23, p < 10(-4), q = 0.095) of RH patients compared with NC. The PCR array data supported previous reports of decreased collagen I/III ratios in skin of RH versus NC (mean = 1.51 ± 0.73 vs. mean = 2.26 ± 0.99; one-sided t test, p = 0.058).


CONCLUSIONS
To our knowledge, this is the first microarray-based analysis to show distinct gene expression profiles between the skin and fascia of RH and NC patients and the first report of an association between GREMLIN1 and incisional hernia formation. Our results suggest that gene expression profiles may act as surrogate markers that stratify patients into different groups at risk for hernia development prior to their initial surgery.
Department of Surgery, The University of Missouri Health Sciences Center, University of Missouri, One Hospital Drive, M610C, Columbia, MO 65212, USA. calalucer@health.missouri.edu
R
R
Calaluce
J W
JW
Davis
S L
SL
Bachman
M M
MM
Gubin
J A
JA
Brown
J D
JD
Magee
T S
TS
Loy
B J
BJ
Ramshaw
U
U
Atasoy
D000328:Adult; D003094:Collagen / Q000096:biosynthesis; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D005205:Fascia / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006555:Hernia, Ventral; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D014945:Wound Healing / Q000235:genetics
C439971:COL3A1 protein, human; D024042:Collagen Type I; D024061:Collagen Type III; C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D003094:Collagen