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NEK6、AURKA、AURKB和PAK1基因在结直肠腺瘤性息肉和结直肠癌中的潜在作用。

The potential role of the NEK6, AURKA, AURKB, and PAK1 genes in adenomatous colorectal polyps and colorectal adenocarcinoma.

作者信息

Kasap Elmas, Gerceker Emre, Boyacıoglu Seda Örenay, Yuceyar Hakan, Yıldırm Hatice, Ayhan Semin, Korkmaz Mehmet

机构信息

Department of Gastroenterology, Medical Faculty, Celal Bayar University, Manisa, Turkey.

Department of Medical Genetics and Medical Biology, Medical Faculty, Celal Bayar University, Manisa, Turkey.

出版信息

Tumour Biol. 2016 Mar;37(3):3071-80. doi: 10.1007/s13277-015-4131-6. Epub 2015 Sep 30.

Abstract

Colorectal adenomatous polyp (CRAP) is a major risk factor for the development of sporadic colorectal cancer (CRC). Histone modifications are one of the epigenetic mechanisms that may have key roles in the carcinogenesis of CRC. The objective of the present study is to investigate the alternations in the defined histone modification gene expression profiles in patients with CRAP and CRC. Histone modification enzyme key gene expressions of the CRC, CRAP, and control groups were evaluated and compared using the reverse transcription PCR (RT-PCR) array method. Gene expression analysis was performed in the CRAP group after dividing the patients into subgroups according to the polyp diameter, pathological results, and morphological parameters which are risk factors for developing CRC in patients with CRAP. PAK1, NEK6, AURKA, AURKB, HDAC1, and HDAC7 were significantly more overexpressed in CRC subjects compared to the controls (p < 0.05). PAK1, NEK6, AURKA, AURKB, and HDAC1 were significantly more overexpressed in the CRAP group compared to the controls (p < 0.005). There were no significant differences between the CRAP and CRC groups with regards to PAK1, NEK6, AURKA, or AURKB gene overexpression. PAK1, NEK6, AURKA, and AURKB were significantly in correlation with the polyp diameter as they were more overexpressed in polyps with larger diameters. In conclusion, overexpressions of NEK6, AURKA, AURKB, and PAK1 genes can be used as predictive markers to decide the colonoscopic surveillance intervals after the polypectomy procedure especially in polyps with larger diameters.

摘要

结直肠腺瘤性息肉(CRAP)是散发性结直肠癌(CRC)发生的主要危险因素。组蛋白修饰是一种表观遗传机制,可能在CRC的致癌过程中起关键作用。本研究的目的是调查CRAP和CRC患者中特定组蛋白修饰基因表达谱的变化。使用逆转录PCR(RT-PCR)阵列方法评估并比较CRC组、CRAP组和对照组的组蛋白修饰酶关键基因表达。在根据息肉直径、病理结果和形态学参数将CRAP患者分为亚组后,对CRAP组进行基因表达分析,这些参数是CRAP患者发生CRC的危险因素。与对照组相比,CRC患者中PAK1、NEK6、AURKA、AURKB、HDAC1和HDAC7的表达明显上调(p < 0.05)。与对照组相比,CRAP组中PAK1、NEK6、AURKA、AURKB和HDAC1的表达明显上调(p < 0.005)。在PAK1、NEK6、AURKA或AURKB基因过表达方面,CRAP组和CRC组之间没有显著差异。PAK1、NEK6、AURKA和AURKB与息肉直径显著相关,因为它们在直径较大的息肉中表达上调更明显。总之,NEK6、AURKA、AURKB和PAK1基因的过表达可作为预测标志物,用于确定息肉切除术后的结肠镜监测间隔,尤其是对于直径较大的息肉。

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