Daniel Rhonda, Wu Qianni, Williams Vernell, Clark Gene, Guruli Georgi, Zehner Zendra
Department of Biochemistry and Molecular Biology, VCU Medical Center and the Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298-0614, USA.
Molecular Diagnostic Laboratory, Department of Pathology, VCU Health System, Virginia Commonwealth University, Richmond, VA 23298-0248, USA.
Int J Mol Sci. 2017 Jun 16;18(6):1281. doi: 10.3390/ijms18061281.
Prostate cancer is the most common non-cutaneous cancer among men; yet, current diagnostic methods are insufficient, and more reliable diagnostic markers need to be developed. One answer that can bridge this gap may lie in microRNAs. These small RNA molecules impact protein expression at the translational level, regulating important cellular pathways, the dysregulation of which can exert tumorigenic effects contributing to cancer. In this study, high throughput sequencing of small RNAs extracted from blood from 28 prostate cancer patients at initial stages of diagnosis and prior to treatment was used to identify microRNAs that could be utilized as diagnostic biomarkers for prostate cancer compared to 12 healthy controls. In addition, a group of four microRNAs (miR-1468-3p, miR-146a-5p, miR-1538 and miR-197-3p) was identified as normalization standards for subsequent qRT-PCR confirmation. qRT-PCR analysis corroborated microRNA sequencing results for the seven top dysregulated microRNAs. The abundance of four microRNAs (miR-127-3p, miR-204-5p, miR-329-3p and miR-487b-3p) was upregulated in blood, whereas the levels of three microRNAs (miR-32-5p, miR-20a-5p and miR-454-3p) were downregulated. Data analysis of the receiver operating curves for these selected microRNAs exhibited a better correlation with prostate cancer than PSA (prostate-specific antigen), the current gold standard for prostate cancer detection. In summary, a panel of seven microRNAs is proposed, many of which have prostate-specific targets, which may represent a significant improvement over current testing methods.
前列腺癌是男性中最常见的非皮肤癌;然而,目前的诊断方法并不充分,需要开发更可靠的诊断标志物。一个可以弥合这一差距的答案可能在于微小RNA。这些小RNA分子在翻译水平上影响蛋白质表达,调节重要的细胞通路,其失调可产生致癌作用,导致癌症发生。在本研究中,对28例处于诊断初期且未接受治疗的前列腺癌患者血液中提取的小RNA进行高通量测序,以确定与12名健康对照相比可作为前列腺癌诊断生物标志物的微小RNA。此外,一组四个微小RNA(miR-1468-3p、miR-146a-5p、miR-1538和miR-197-3p)被确定为后续qRT-PCR验证的标准化标准。qRT-PCR分析证实了七种失调最严重的微小RNA的测序结果。四种微小RNA(miR-127-3p、miR-204-5p、miR-329-3p和miR-487b-3p)在血液中的丰度上调,而三种微小RNA(miR-32-5p、miR-20a-5p和miR-454-3p)的水平下调。对这些选定微小RNA的受试者工作曲线进行数据分析,结果显示与前列腺癌的相关性优于目前前列腺癌检测的金标准——前列腺特异性抗原(PSA)。总之,提出了一组七种微小RNA,其中许多具有前列腺特异性靶点,这可能代表了对当前检测方法的显著改进。