Department of Surgery, The University of Missouri Health Sciences Center, University of Missouri, One Hospital Drive, M610C, Columbia, MO 65212, USA.
Hernia. 2013 Apr;17(2):193-202. doi: 10.1007/s10029-012-0923-4. Epub 2012 May 31.
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.
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.
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).
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.
尽管人们已经了解切口疝形成的情境风险因素，但用于确定哪些人最容易患上切口疝的方法并不可靠。我们假设复发性切口疝患者可能具有独特的基因表达谱。
从 15 名无疝病史的正常对照（NC）患者和 18 名接受复发性切口疝（RH）修复的患者中收集皮肤和完整筋膜。对 NC（n=8）和 RH（n=9）患者进行全基因组微阵列芯片微阵列分析。这些样本进一步使用包含纤维化相关基因的通路特异性 PCR 阵列进行研究。
微阵列数据分析显示，RH 和 NC 患者的基因表达谱存在明显差异。皮肤中有 167 个基因和筋膜中有 7 个基因表达不同，其中 8 个基因直接参与胶原蛋白合成。特别是，骨形态发生蛋白拮抗剂 1（GREMLIN1）在 RH 患者的皮肤（fold=0.49，p<10(-7)，q=0.0009）和筋膜（fold=0.23，p<10(-4)，q=0.095）中表达下调。PCR 阵列数据支持先前关于 RH 患者皮肤中胶原 I/III 比值降低的报道（平均值=1.51±0.73 与平均值=2.26±0.99；单侧 t 检验，p=0.058）。
据我们所知，这是首次基于微阵列的分析，显示 RH 和 NC 患者皮肤和筋膜之间存在明显的基因表达谱差异，也是首次报道 GREMLIN1 与切口疝形成之间存在关联。我们的研究结果表明，基因表达谱可能作为替代标志物，在患者首次手术前将其分层为不同的疝发生风险组。
