Dipeptidase 1 (DPEP1) is a marker for the transition from low-grade to high-grade intraepithelial neoplasia and an adverse prognostic factor in colorectal cancer.

Dipeptidase 1 (DPEP1) is a marker for the transition from low-grade to high-grade intraepithelial neoplasia and an adverse prognostic factor in colorectal cancer.
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DOI:
10.1038/bjc.2013.363
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发表时间:
2013-08-06
影响因子:
8.8
通讯作者:
Sipos B
Sipos B
中科院分区:
医学1区
文献类型:
--
作者:
Eisenach PA;Soeth E;Röder C;Klöppel G;Tepel J;Kalthoff H;Sipos B

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结直肠癌(CRC)是全球癌症相关死亡的第二大原因。提高对其分子机制的理解和促进早期检测的CRC特异性生物标志物的表征被认为可以增加总生存期。基因表达的微阵列和系列分析(SAGE)的荟萃分析已被执行,以确定差异调控的基因在CRC。发现二肽酶1(DPEP 1/MDP/RDP)和Syntenin-2(SDCBP 2/SITAC 18)在肿瘤组织中与正常粘膜相比差异表达。通过免疫组织化学以及部分免疫印迹和实时PCR,在由87份正常粘膜样本、20份增生性息肉、46份伴有低度和高度上皮内瘤变(SEN)的CR腺瘤以及217份有充分证据的CRC组成的验证集中评估了DPEP 1的表达。与正常粘膜相比,DPEP 1的表达在人CRC组织样品中特异性增加(P<0.0001,Mann-Whitney U-检验),显示与低级别IEN相比,高级别中的显著上调。此外,发现高DPEP 1表达与组织学分期(P<0.0001,卡方检验)以及定位(P<0.0001,卡方检验)强烈相关,并且已被认为是独立的不良预后因素,显示出显著的预后值,ROC(受试者操作特征)-AUC为0.9230。二肽酶1已被确定为高级别肠内营养不良和结直肠癌的一个很好的标志物,因此可以应用于早期肿瘤病变的筛查和预后分层。
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Improvements in the understanding of its molecular mechanism and the characterisation of CRC-specific biomarkers facilitating early detection are considered to increase overall survival. A meta-analysis of microarray and Serial Analysis of Gene Expression (SAGE) has been performed to identify differentially regulated genes in CRC. Dipeptidase 1 (DPEP1/MDP/RDP) and Syntenin-2 (SDCBP2/SITAC18) were found to be differentially expressed in tumour tissue compared with normal mucosa. Expression of DPEP1 was assessed in a validation set of 87 normal mucosa samples, 20 hyperplastic polyps, 46 CR adenomas with low- and high-grade intraepithelial neoplasia (IEN) and 217 well-documented CRCs by immunohistochemistry and partially by immunoblotting and real-time PCR. Expression of DPEP1 was specifically increased in human CRC tissue samples compared with normal mucosa (P<0.0001, Mann–Whitney U-test), showing a striking upregulation in high-grade compared with low-grade IEN. Furthermore, high DPEP1 expression was found to strongly correlate with histological stage (P<0.0001, chi-square test) as well as localisation (P<0.0001, chi-square test) and has been recognised as an independent adverse prognostic factor, showing significant prognostic values with an ROC (receiver operating characteristic)-AUC of 0.9230. Dipeptidase 1 has been identified as an excellent marker of high-grade IEN and CRC, and may thus be applied for screening of early neoplastic lesions and for prognostic stratification.
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