Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Hernia
Published in: Hernia 2/2013

Open Access 01-04-2013 | Original Article

Incisional hernia recurrence through genomic profiling: a pilot study

Authors: R. Calaluce, J. W. Davis, S. L. Bachman, M. M. Gubin, J. A. Brown, J. D. Magee, T. S. Loy, B. J. Ramshaw, U. Atasoy

Published in: Hernia | Issue 2/2013

Login to get access

Abstract

Purpose

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).

Conclusion

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.
Appendix
Available only for authorised users
Literature
1.
2.
Awad ZT, Puri V, LeBlanc K, Stoppa R, Fitzgibbons RJ Jr, Iqbal A, Filipi CJ (2005) Mechanisms of ventral hernia recurrence after mesh repair and a new proposed classification. J Am Coll Surg 201:132–140PubMedCrossRef
3.
4.
Klinge U, Zheng H, Si ZY, Schumpelick V, Bhardwaj R, Klosterhalfen B (1999) Synthesis of type I and III collagen, expression of fibronectin and matrix metalloproteinases-1 and -13 in hernial sac of patients with inguinal hernia. Int J Surg Investig 1:219–227PubMed
5.
Klinge U, Zheng H, Si Z, Schumpelick V, Bhardwaj RS, Muys L, Klosterhalfen B (1999) Expression of the extracellular matrix proteins collagen I, collagen III and fibronectin and matrix metalloproteinase-1 and -13 in the skin of patients with inguinal hernia. Eur Surg Res 31:480–490PubMedCrossRef
6.
Klinge U, Si ZY, Zheng H, Schumpelick V, Bhardwaj RS, Klosterhalfen B (2000) Abnormal collagen I to III distribution in the skin of patients with incisional hernia. Eur Surg Res 32:43–48PubMedCrossRef
7.
Rosch R, Junge K, Knops M, Lynen P, Klinge U, Schumpelick V (2003) Analysis of collagen-interacting proteins in patients with incisional hernias. Langenbecks Arch Surg 387:427–432PubMed
8.
White B, Osier C, Gletsu N, Jeansonne L, Baghai M, Sherman M, Smith CD, Ramshaw B, Lin E (2007) Abnormal primary tissue collagen composition in the skin of recurrent incisional hernia patients. Am Surg 73:1254–1258PubMed
9.
Liem MS, van der Graaf Y, Beemer FA, van Vroonhoven TJ (1997) Increased risk for inguinal hernia in patients with Ehlers-Danlos syndrome. Surgery 122:114–115PubMedCrossRef
10.
Rowe DW, Shapiro JR, Poirier M, Schlesinger S (1985) Diminished type I collagen synthesis and reduced alpha 1(I) collagen messenger RNA in cultured fibroblasts from patients with dominantly inherited (type I) osteogenesis imperfecta. J Clin Invest 76:604–611PubMedCrossRef
11.
Deak SB, Ricotta JJ, Mariani TJ, Deak ST, Zatina MA, Mackenzie JW, Boyd CD (1992) Abnormalities in the biosynthesis of type III procollagen in cultured skin fibroblasts from two patients with multiple aneurysms. Matrix 12:92–100PubMedCrossRef
12.
Heath JD, Cox D, Goralski T, Retief J (2007) NuGen’s WT-Ovation FFPE System coupled with a novel labeling protocol enables genome-wide gene expression profiling of FFPE sample on the Illumina BeadArray platform. Application Note #2. NuGen Technologies
13.
Calaluce R, Gubin MM, Davis JW, Magee JD, Chen J, Kuwano Y, Gorospe M, Atasoy U (2010) The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer. BMC Cancer 10:126–140PubMedCrossRef
14.
Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3:Article3
15.
Ramos-Vara JA, Beissenherz ME (2000) Optimization of immunohistochemical methods using two different antigen retrieval methods on formalin-fixed paraffin-embedded tissues: experience with 63 markers. J Vet Diagn Invest 12:307–311PubMedCrossRef
16.
Gubin MM, Calaluce R, Davis JW, Magee JD, Strouse CS, Shaw DP, Ma L, Brown A, Hoffman T, Rold TL, Atasoy U (2010) Overexpression of the RNA binding protein HuR impairs tumor growth in triple negative breast cancer associated with deficient angiogenesis. Cell Cycle 9:3337–3346PubMedCrossRef
17.
Pelch KE, Schroder AL, Kimball PA, Sharpe-Timms KL, Davis JW, Nagel SC (2010) Aberrant gene expression profile in a mouse model of endometriosis mirrors that observed in women. Fertil Steril 93:1615–1627, e1817
18.
Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B 57:289–300
19.
Avsian-Kretchmer O, Hsueh AJ (2004) Comparative genomic analysis of the eight-membered ring cystine knot-containing bone morphogenetic protein antagonists. Mol Endocrinol 18:1–12PubMedCrossRef
20.
Bucknall TE, Cox PJ, Ellis H (1982) Burst abdomen and incisional hernia: a prospective study of 1129 major laparotomies. Br Med J (Clin Res Ed) 284:931–933CrossRef
21.
Greenall MJ, Evans M, Pollock AV (1980) Midline or transverse laparotomy? A random controlled clinical trial. Part I: Influence on healing. Br J Surg 67:188–190PubMedCrossRef
22.
Gys T, Hubens A (1989) A prospective comparative clinical study between monofilament absorbable and non-absorbable sutures for abdominal wall closure. Acta Chir Belg 89:265–270PubMed
23.
Hsu DR, Economides AN, Wang X, Eimon PM, Harland RM (1998) The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. Mol Cell 1:673–683PubMedCrossRef
24.
Topol LZ, Modi WS, Koochekpour S, Blair DG (2000) DRM/GREMLIN (CKTSF1B1) maps to human chromosome 15 and is highly expressed in adult and fetal brain. Cytogenet Cell Genet 89:79–84PubMedCrossRef
25.
McMahon R, Murphy M, Clarkson M, Taal M, Mackenzie HS, Godson C, Martin F, Brady HR (2000) IHG-2, a mesangial cell gene induced by high glucose, is human gremlin. Regulation by extracellular glucose concentration, cyclic mechanical strain, and transforming growth factor-beta1. J Biol Chem 275:9901–9904PubMedCrossRef
26.
Lappin DW, McMahon R, Murphy M, Brady HR (2002) Gremlin: an example of the re-emergence of developmental programmes in diabetic nephropathy. Nephrol Dial Transpl 17(Suppl 9):65–67CrossRef
27.
Murphy M, McMahon R, Lappin DW, Brady HR (2002) Gremlins: is this what renal fibrogenesis has come to? Exp Nephrol 10:241–244PubMedCrossRef
28.
Meyringer R, Neumann E, Judex M, Landthaler M, Kullmann F, Scholmerich J, Gay S, Tarner IH, Distler O, Muller-Ladner U (2007) Analysis of gene expression patterns in systemic sclerosis fibroblasts using RNA arbitrarily primed-polymerase chain reaction for differential display. J Rheumatol 34:747–753PubMed
29.
Sneddon JB, Zhen HH, Montgomery K, van de Rijn M, Tward AD, West R, Gladstone H, Chang HY, Morganroth GS, Oro AE et al (2006) Bone morphogenetic protein antagonist gremlin 1 is widely expressed by cancer-associated stromal cells and can promote tumor cell proliferation. Proc Natl Acad Sci USA 103:14842–14847PubMedCrossRef
30.
Fricke M, Langer C, Brunner E, Sakai LY, Fuzesi L, Reinhardt DP, Quondamatteo F (2008) Fibrillin-1 in incisional hernias: an immunohistochemical study in scar and non-scar regions of human skin and muscle fasciae. J Anat 212:674–685PubMedCrossRef
Metadata
Title
Incisional hernia recurrence through genomic profiling: a pilot study
Authors
R. Calaluce
J. W. Davis
S. L. Bachman
M. M. Gubin
J. A. Brown
J. D. Magee
T. S. Loy
B. J. Ramshaw
U. Atasoy
Publication date
01-04-2013
Publisher
Springer-Verlag
Published in
Hernia / Issue 2/2013
Print ISSN: 1265-4906
Electronic ISSN: 1248-9204
DOI
https://doi.org/10.1007/s10029-012-0923-4

Other articles of this Issue 2/2013

Hernia 2/2013 Go to the issue

Case Report

Strangulated perforated hiatus hernia due to pyloric stenosis

Erratum

Erratum to: True-FISP MRI in diagnosis of postoperative hernia recurrence: a brief report

Case Report

A rare cause of mechanical bowel obstruction: mesh migration

Original Article

Laparoscopic repair of incarcerated inguinal hernia. A safe and effective procedure to adopt in children

Original Article

Laparoscopic herniotomy in children: prospective assessment of tertiary center experience in a developing country

Review

A meta-analysis comparing tacker mesh fixation with suture mesh fixation in laparoscopic incisional and ventral hernia repair