Liu Xiangxiang, Xu Tao, Hu Xiuxiu, Chen XiaoXiang, Zeng Kaixuan, Sun Li, Wang Shukui
Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Cancer Manag Res. 2018 Apr 24;10:857-865. doi: 10.2147/CMAR.S158016. eCollection 2018.
Globally, colorectal cancer (CRC) is one of the most common cancers with high mortality. Although CRC patients in stages I-II are curable after surgical resection, due to the lack of sensitive and specific biomarkers, many patients are in the advanced stages when diagnosed. This study aimed to investigate whether circulating miRNAs in plasma could act as biomarkers for early CRC diagnosis.
All healthy subjects and patients were from Nanjing First Hospital. We first selected 2 differential miRNAs by integrated analysis of 4 Gene Expression Omnibus (GEO) data sets and The Cancer Genome Atlas (TCGA) database. Next, the expression of these 2 miRNAs in tissue and plasma samples were examined through quantitative real-time polymerase chain reaction. Training phase and validation phase were designed to investigate the diagnostic utility of these differential miRNAs using receiver operating characteristic (ROC) curve analysis.
After integrated analysis of 4 GEO and TCGA databases, upregulated miR-182 and miR-20a were selected to further investigate their diagnostic potential for CRC. We discovered that miR-182 and miR-20a were upregulated in CRC tissue and plasma and that circulating miR-182 and miR-20a in the plasma of CRC patients were tumor derived. The area under the ROC curve (AUC) of circulating miR-182 was 0.929 (95% CI 0.875-0.983) in the training phase and 0.891 (95% CI 0.821-0.961) in the validation phase. The AUC of circulating miR-20a expression was 0.801 (95% CI 0.695-0.906) in the training phase and 0.736 (95% CI 0.631-0.842) in the validation phase.
Circulating miR-182 is a novel potential biomarker for early CRC diagnosis.
在全球范围内,结直肠癌(CRC)是最常见且死亡率高的癌症之一。尽管I-II期CRC患者在手术切除后可治愈,但由于缺乏敏感且特异的生物标志物,许多患者在确诊时已处于晚期。本研究旨在调查血浆中循环miRNA是否可作为早期CRC诊断的生物标志物。
所有健康受试者和患者均来自南京第一医院。我们首先通过对4个基因表达综合数据库(GEO)数据集和癌症基因组图谱(TCGA)数据库进行综合分析,筛选出2种差异miRNA。接下来,通过定量实时聚合酶链反应检测这2种miRNA在组织和血浆样本中的表达。设计训练阶段和验证阶段,使用受试者工作特征(ROC)曲线分析来研究这些差异miRNA的诊断效用。
在对4个GEO和TCGA数据库进行综合分析后,上调的miR-182和miR-20a被选中,以进一步研究它们对CRC的诊断潜力。我们发现miR-182和miR-20a在CRC组织和血浆中上调,且CRC患者血浆中的循环miR-182和miR-20a来源于肿瘤。在训练阶段,循环miR-182的ROC曲线下面积(AUC)为0.929(95%CI 0.875-0.983),在验证阶段为0.891(95%CI 0.821-0.961)。循环miR-20a表达的AUC在训练阶段为0.801(95%CI 0.695-0.906),在验证阶段为0.736(95%CI 0.631-0.842)。
循环miR-182是早期CRC诊断的一种新型潜在生物标志物。