遗传性非息肉性大肠癌生物标志物的血清miRNAs的筛选

Serum microRNAs as promising novel biomarkers for hereditary nonpolyposis colorectal cancer

目的:应用microRNA(miRNA)芯片筛选及qRT-PCR技术检测可作为遗传性非息肉性大肠癌生物标志物的血清miRNAs.方法:选取4个遗传性非息肉性大肠癌患者及3个无家族史正常人的血清miRNAs进行miRNA芯片检测,再用q-PCR方法对于芯片结果进行验证.结果:miRNA芯片筛查出57个上调及30个下调miRNAs,在这些差异性表达的miRNAs中选出8个较为理想的miRNAs作进一步研究,运用3个靶基因预测软件预测靶基因后取交集,得到294个靶基因,均是属于mir-20a-5p,mir-548b-5p和mir-548as-3p的靶基因.用qPCR的方法在标本中进行验证发现mir-548as-3p的表达情况符合芯片结果-在遗传性非息肉性大肠癌患者血清中表达上调.结论:血清miRNAs在遗传性非息肉性大肠癌患者中的差异性表达,mir-548as-3p可能为遗传性非息肉性大肠癌非侵入性的生物标志物.

AIM： To screen and identify serum microRNAs （miRNAs） that might be used as promising biomarkers for hereditary nonpolyposis colorectal cancer using miRNA array and qRT-PCR. METHODS： Four serum samples from patients with hereditary nonpolyposis colorectal cancer and three serum samples from healthy controlswere used to identify potential markers by miRNA array. The results of miRNA array were confirmed by qRT-PCR. RESULTS： We found 57 up-regulated miRNAs and 30 down-regulated miRNAs by miRNA array, and 8 miRNAs were chosen for further analysis. Three target gene prediction programs were used to predict target genes of these 8 miRNAs, and 294 genes were predicted, all of which were target genes of mir-20a-5p, mir-548b-5p and mir-548as-3p. qPCR analysis confirmed that serum mir-548as-3p was significantly higher in patients with hereditary nonpolyposis colorectal cancer. CONCLUSION： Our study demonstrates that serum miRNAs are differentially expressed in patients with hereditary nonpolyposis colorectal cancer, and that mir-548as-3p can potentially serve as a noninvasive biomarker for this disease.