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对微小RNA群体进行广泛筛选后发现,hsa-miR-375和hsa-miR-133a-3p是人类直肠癌和结肠癌的选择性标志物。

Extensive screening of microRNA populations identifies hsa-miR-375 and hsa-miR-133a-3p as selective markers for human rectal and colon cancer.

作者信息

Weber David, Amar Laurence, Gödde Daniel, Prinz Christian

机构信息

Lehrstuhl für Innere Medizin 1, University of Witten, 42283 Wuppertal, Germany.

Institut des Neurosciences Paris-Saclay (Neuro-PSI)-CNRS UMR 9197, Université Paris-Saclay/Paris-Sud, 91405 Orsay, France.

出版信息

Oncotarget. 2018 Jun 5;9(43):27256-27267. doi: 10.18632/oncotarget.25535.

Abstract

MicroRNAs (miRNAs) are ∼22-nt molecules exerting control of protein expression in cancer tissues. The current study determined the full spectrum of miRNA dysregulation in freshly isolated human colon or rectal cancer biopsies as well as in controls of healthy adjacent tissue (total of = 100) using an Illumina sequencing technology. In this work, we aimed to identify miRNAs that may serve as future marker to discern between these two subtypes. DESeq2 analysis revealed 53 significantly dysregulated miRNAs in colon cancer, 67 miRNAs in rectal cancer, and 97 miRNAs in both at a value < 0.05 and ≥ 10 read counts. 65% of miRNAs were upregulated in colon as well as rectal cancer. Highest significant dysregulation ( < 0.00001) was detected for hsa-miR-21-5p, -215-5p and -378a in both colon and rectal cancer. Among the group of miRNAs with < 0.05 and more than 2-fold expression differences, hsa-miR-375 was detected in rectal cancer only, and hsa-miR-133a-3p only in colon cancer. Receiver operating characteristic (ROC) analysis confirmed highly distinct sensitivities for hsa-miR-375 to detect rectal cancer (area under the curve (AUC): 0.9), while hsa-miR-133a-3p (AUC: 0.89) had the highest sensitivity for detecting colon cancer. We conclude that hsa-miR-375 and hsa-miR-133a-3p may serve as new markers of rectal or colon cancer and should be further investigated to search for different etiologies of colorectal cancer.

摘要

微小RNA(miRNA)是一类长度约为22个核苷酸的分子,可调控癌症组织中的蛋白质表达。本研究使用Illumina测序技术,确定了新鲜分离的人类结肠癌或直肠癌活检组织以及健康邻近组织对照(共100例)中miRNA失调的全貌。在这项工作中,我们旨在鉴定可能作为区分这两种亚型的未来标志物的miRNA。DESeq2分析显示,在结肠癌中有53种显著失调的miRNA,直肠癌中有67种,两者共有97种,其P值<0.05且读数计数≥10。65%的miRNA在结肠癌和直肠癌中均上调。在结肠癌和直肠癌中,hsa-miR-21-5p、-215-5p和-378a的失调最为显著(P<0.00001)。在P<0.05且表达差异超过2倍的miRNA组中,hsa-miR-375仅在直肠癌中检测到,hsa-miR-133a-3p仅在结肠癌中检测到。受试者工作特征(ROC)分析证实,hsa-miR-375检测直肠癌的敏感性非常高(曲线下面积(AUC):0.9),而hsa-miR-133a-3p(AUC:0.89)检测结肠癌的敏感性最高。我们得出结论,hsa-miR-375和hsa-miR-133a-3p可能作为直肠癌或结肠癌的新标志物,应进一步研究以寻找结直肠癌的不同病因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc21/6007480/588cffdf4316/oncotarget-09-27256-g001.jpg

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