Sadr-Nabavi Ariane, Bouromand-Noughabi Samaneh, Tayebi-Meybodi Naser, Dadkhah Kimia, Amini Nafiseh, Meindl Alfons, Abbaszadegan Mohammad Reza
Medical Genetic Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Human Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2021 Apr;24(4):444-450. doi: 10.22038/IJBMS.2021.46422.10720.
Dermatopontin (DPT) is an extracellular matrix protein that plays roles in increasing the activity of transforming growth factor-β (TGF-β) and induction of cell quiescence. These roles suggest a tumor suppressor function for DPT. This study aimed to investigate changes in DPT gene expression in colorectal cancer providing a better understanding of its carcinogenesis.
We used Matched Tumor/Normal Expression Array and Cancer Profiling Arrays I containing 34 and 7 cases of colorectal cancer and their matched controls, respectively, to test DPT expression. In addition, 38 newly diagnosed cases of colorectal cancer were enrolled and their fresh colonic tumoral and normal specimens were obtained. DPT mRNA expression was analyzed using real-time PCR. In cases with DPT under expression, exonic regions of the DPT gene were sequenced using the Sanger method.
In array samples, DPT expression was decreased in 82.9% (34/41), increased in 12.2% (5/41), and had no changes in 4.9% (2/41). DPT was decreased in 14 fresh samples (36.8%), while 12 cases (31.6%) showed overexpression and the others had no changes. DPT expression showed no significant difference among various tumor grades and stages. The frequencies of DPT overexpression were higher in tumors having lymph node involvement (47.7% vs 28%, =0.59). In 2 cases mutations were detected that may be responsible for decreased expression of DPT.
The similarities between changing patterns of DPT and TGF-β expression in colorectal cancer demonstrate that DPT may act as a pre-receptor component of the TGF-β signaling pathway in colon carcinogenesis.
皮肤桥蛋白(DPT)是一种细胞外基质蛋白,在增强转化生长因子-β(TGF-β)活性和诱导细胞静止方面发挥作用。这些作用提示DPT具有肿瘤抑制功能。本研究旨在调查结直肠癌中DPT基因表达的变化,以更好地了解其致癌机制。
我们分别使用包含34例和7例结直肠癌及其配对对照的配对肿瘤/正常表达阵列和癌症分析阵列I来检测DPT表达。此外,纳入38例新诊断的结直肠癌病例,并获取其新鲜的结肠肿瘤和正常标本。使用实时PCR分析DPT mRNA表达。对于DPT表达下调的病例,采用桑格法对DPT基因的外显子区域进行测序。
在阵列样本中,82.9%(34/41)的DPT表达降低,12.2%(5/41)升高,4.9%(2/41)无变化。14个新鲜样本(36.8%)中DPT降低,12例(31.6%)显示过表达,其他样本无变化。DPT表达在不同肿瘤分级和分期之间无显著差异。在有淋巴结转移的肿瘤中,DPT过表达的频率更高(47.7%对28%,P = 0.59)。在2例中检测到可能导致DPT表达降低的突变。
结直肠癌中DPT和TGF-β表达变化模式的相似性表明,DPT可能在结肠癌发生过程中作为TGF-β信号通路的前受体成分发挥作用。