Sakurai Minako, Masuda Mariko, Miki Yasuhiro, Hirakawa Hisashi, Suzuki Takashi, Sasano Hironobu
1 Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi - Japan.
Int J Biol Markers. 2015 May 26;30(2):e190-9. doi: 10.5301/jbm.5000141.
New molecular markers related to prognosis and/or clinical outcome have been extensively studied in breast cancer. In particular, microRNA (miRNA) has attracted the interest of both basic and clinical investigators as one of the promising molecular markers of breast cancer patients. MiRNAs are a class of short noncoding RNAs that regulate mRNAs at posttranscriptional level and are deregulated in various human malignancies. Previous studies have reported that miRNAs were stably conserved in 10% formalin-fixed paraffin-embedded tissues without significant degradation, in contrast to more fragile RNA.
Therefore, in this study, we examined 21 surgical breast cancer specimens using the Human Cancer microRNA PCR Array system (QIAGEN) to explore potential molecular targets of miRNAs.
Profiling of miRNA expression in archival materials demonstrated that a group of deregulated miRNAs was associated with clinicopathological parameters of the patients, such as Ki-67, HER2, ER and PR. For instance, an abundant expression of multiple let-7 miRNA family, also known as tumor suppressor, was detected in low Ki-67 and HER2 groups. Elevated expression of 8 miRNAs overlapped between Ki-67+/HER2+/ER+/PR+ groups, including several known oncogenic miRNAs such as miR-148b, miR-15b, miR-200c, miR-150, miR-191, miR-96, miR-25 and miR-21.
These results all indicated that when analyzing miRNAs in surgical pathology specimens of breast cancer as a biomarker, they should be examined as a cluster through miRNA profiling, rather than relying on the analysis of a single miRNA.
与乳腺癌预后和/或临床结局相关的新分子标志物已得到广泛研究。尤其是,微小RNA(miRNA)作为乳腺癌患者有前景的分子标志物之一,吸引了基础和临床研究人员的关注。miRNA是一类短的非编码RNA,在转录后水平调节mRNA,并且在各种人类恶性肿瘤中表达失调。先前的研究报道,与更易降解的RNA相比,miRNA在10%中性福尔马林固定石蜡包埋组织中稳定保守,无明显降解。
因此,在本研究中,我们使用人类癌症miRNA PCR阵列系统(QIAGEN)检测了21例手术切除的乳腺癌标本,以探索miRNA的潜在分子靶点。
存档材料中miRNA表达谱分析表明,一组表达失调的miRNA与患者的临床病理参数相关,如Ki-67、HER2、雌激素受体(ER)和孕激素受体(PR)。例如,在低Ki-67和HER2组中检测到多个也被称为肿瘤抑制因子的let-7 miRNA家族的丰富表达。8种miRNA的表达升高在Ki-67+/HER2+/ER+/PR+组中重叠,包括几种已知的致癌miRNA,如miR-148b、miR-15b、miR-200c、miR-150、miR-191、miR-96、miR-25和miR-21。
这些结果均表明,当将乳腺癌手术病理标本中的miRNA作为生物标志物进行分析时,应通过miRNA谱分析将它们作为一个簇进行检测,而不是依赖于单个miRNA的分析。