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散发性结直肠癌中 MMR 基因的表达模式。

MMR gene expression pattern in sporadic colorectal cancer.

机构信息

Department of Molecular and Cellular Biology, University of Medicine and Pharmacy, 2 Petru Rares Str., Craiova, Romania.

出版信息

J Gastrointestin Liver Dis. 2010 Jun;19(2):155-9.

Abstract

BACKGROUND AND AIMS

Colorectal carcinoma is the second leading cause of death by cancer in Europe as its incidence increases with life span. Continuing research to detect new highly sensitive and specific noninvasive biomarkers is essential. The aim of this study was to compare 9 mismatching repair (MMR) genes activation levels in normal, polyp and malignant tissues in order to detect a MMR gene expression pattern in sporadic colorectal malignant pathology.

METHODS

MMR mRNA levels were evaluated in tumor-normal tissue paired samples and polyps collected from 29 patients undergoing standard surgical procedures with curative intention. Real-Time quantitative Reverse Transcription PCR (qRT PCR) with TaqMan probes specific to ANKRD17, EXO1, MLH1, MLH3, MSH2, MSH3, MSH4, MSH5, MSH6 gene transcripts were used.

RESULTS

The general tendency observed was a lower mRNA level of MMR genes in tumor samples compared with the normal tissue, with the exception of EXO1 gene. The number of patients that showed a higher expression of MMR genes in normal tissue was significantly greater than the number of patients that showed a higher expression inside the tumor (p=0.0024). ANKRD17 mRNA levels were higher in normal tissue than in tumor for 16 cases, by contrast with only 6 cases of higher mRNA levels in tumor.

CONCLUSIONS

ANKRD17 mRNA appears to be the most sensitive target and may have a potential value as an additional marker for the existing multitarget assay panel for colorectal cancer detection.

摘要

背景与目的

结直肠癌是欧洲第二大癌症死因,其发病率随寿命的延长而增加。继续研究以发现新的高度敏感和特异的非侵入性生物标志物至关重要。本研究旨在比较正常、息肉和恶性组织中 9 个错配修复(MMR)基因的激活水平,以检测散发性结直肠恶性病变中的 MMR 基因表达模式。

方法

对 29 例接受根治性标准手术的患者的肿瘤-正常组织配对样本和息肉进行 MMR mRNA 水平评估。采用 TaqMan 探针的实时定量逆转录 PCR(qRT-PCR)检测 ANKRD17、EXO1、MLH1、MLH3、MSH2、MSH3、MSH4、MSH5、MSH6 基因转录本。

结果

观察到的一般趋势是肿瘤样本中 MMR 基因的 mRNA 水平低于正常组织,除了 EXO1 基因。在正常组织中显示 MMR 基因表达更高的患者数量明显多于在肿瘤中显示更高表达的患者数量(p=0.0024)。ANKRD17 的 mRNA 水平在正常组织中高于肿瘤组织的有 16 例,而肿瘤组织中更高的 mRNA 水平仅有 6 例。

结论

ANKRD17 mRNA 似乎是最敏感的靶标,可能作为现有的结直肠癌检测多靶标检测 panel 的附加标志物具有潜在价值。

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