Brînzan Costel, Aşchie Mariana, Cozaru Georgeta, Dumitru Eugen, Mitroi Anca
Pathology Department, Sf. Apostol Andrei Clinical Emergency County Hospital.
CEDMOG Center, Ovidius University.
Medicine (Baltimore). 2020 Aug 28;99(35):e21895. doi: 10.1097/MD.0000000000021895.
MicroRNAs (miRNAs) refers to a small, short non-coding RNA of endogenous class. They have shown to have an increasingly altered expression in many types of cancer, including colorectal cancer (CRC).In the present study, miRNA TaqManMGB and qRT-PCR was used to quantify the expression and clinical significance of 3 mature human miRNA in 82 pairs of colorectal adenocarcinoma tissues and normal adjacent tissue samples (NATS) collected from patients of the south-east part of Romania. Differences between CRC and NATS were analyzed using Wilcoxon test, while correlations between miRNAs expression levels and clinicopathological features were examined using non-parametric tests. In addition, the ability of selected miRNAs to function as biomarkers and, as potential indicators in CRC prognosis was also examined.When the miRNA expression was compared in CRC related NATS, miR-143, and miR-145 were significantly underexpressed (4.99 ± -1.02 vs -5.66 ± -1.66, P < .001; -4.85 ± -0.59 vs -9.27 ± -1.51, P < .001, respectively), while the pattern of miR-92a was significantly overexpressed (-5.55 ± -2.83 vs -4.92 ± -2.44, P < .001). Moreover, the expression levels of selected miRNAs were identified to be correlated with gradual increases in fold change expression with the depth of tumor invasion, lymph node invasion, and maximal increases with distant metastasis. Furthermore, the receiver operating characteristic analysis demonstrated that potential diagnostic of miR-143, miR-145, and miR-92a in discriminating CRC from NATS, with the area under the curve of 0.74, 0.85, and 0.84 respectively. The Kaplan-Meier and the log-rank test showed that a high level of miR-92a and low levels of miR-143 and miR-145 predicted poor survival rate in our cohorts.In conclusion, we can summarize that miR-145 and miR-143 are decreased, while miR-92 is increased in CRC compared to NATS, and associated with different stages of CRC pathogenesis. Thus, the expression of selected miRNAs can represent potential diagnostic and prognostic tools in patients with CRC from Romania.
微小RNA（miRNA）是一类内源性的小的非编码RNA。它们在包括结直肠癌（CRC）在内的多种癌症中显示出表达改变日益增多。在本研究中，采用miRNA TaqManMGB和qRT-PCR技术对从罗马尼亚东南部患者收集的82对结直肠腺癌组织和正常相邻组织样本（NATS）中3种成熟人类miRNA的表达及其临床意义进行定量分析。使用Wilcoxon检验分析CRC与NATS之间的差异，同时使用非参数检验检查miRNA表达水平与临床病理特征之间的相关性。此外，还研究了所选miRNA作为生物标志物的功能以及作为CRC预后潜在指标的能力。当比较CRC相关NATS中的miRNA表达时，miR-143和miR-145显著低表达（分别为4.99± -1.02对 -5.66± -1.66，P <.001；-4.85± -0.59对 -9.27± -1.51，P <.001），而miR-92a的模式显著高表达（-5.55± -2.83对 -4.92± -2.44，P <.001）。此外，所选miRNA的表达水平被确定与肿瘤浸润深度、淋巴结浸润的倍数变化表达逐渐增加以及远处转移时的最大增加相关。此外，受试者工作特征分析表明，miR-143、miR-145和miR-92a在区分CRC与NATS方面具有潜在诊断价值，曲线下面积分别为0.74、0.85和0.84。Kaplan-Meier和对数秩检验表明，高水平的miR-92a以及低水平的miR-143和miR-145预示着我们队列中的生存率较差。总之，我们可以总结出，与NATS相比，CRC中miR-145和miR-143降低，而miR-92升高，并且与CRC发病机制的不同阶段相关。因此，所选miRNA的表达可以代表罗马尼亚CRC患者潜在的诊断和预后工具。
