Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer
Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer
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DOI：
10.1093/annonc/mdw279
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发表时间：
2016-10-01
影响因子：
50.5
通讯作者：
Kusunoki, M.
中科院分区：
文献类型：
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作者：
Imaoka, H.;Toiyama, Y.;Kusunoki, M.
我们综合的miRNA微阵列分析确定了对照组和腺瘤或CRC之间血清miRNA表达谱的显著差异。尤其是miR-1290在大肠腺瘤和大肠癌患者血清中的表达显著上调，是一种很有前途的、基于血清的非侵袭性生物标志物，可用于大肠癌的检测和预后判断。本研究旨在寻找一种新的血清miRNA生物标志物用于早期检测和/或评估结直肠癌患者的预后。接下来，为了验证候选miRNA是否具有分泌潜力，我们从2个CRC细胞系中筛选培养基中的miRNA表达水平，然后对12个IV期CRC、12个腺瘤和12个对照受试者进行血清分析。此后，我们验证了候选miRNA在179例原发性CRC组织中的表达，以及来自211例CRC、56例腺瘤和57例对照受试者的独立队列的血清样本。通过微阵列分析，我们在结直肠腺瘤和癌症患者的血清中鉴定出显著较高水平的miRNA-1290（miR-1290）。我们在训练队列中验证了CRC患者血清中miR-1290的过表达。在验证队列中，血清miR-1290水平在结直肠腺瘤（P < 0.0001）和癌症（P < 0.0001）患者中显著上调。血清miR-1290水平可以将腺瘤[曲线下面积（AUC）= 0.718]和CRC患者（AUC = 0.830）与正常受试者强有力地区分开。血清和组织中miR-1290的高表达与肿瘤的侵袭性和不良预后显著相关。此外，血清miR-1290水平是一个独立的预后因素[风险比（HR）= 4.51; 95%置信区间（CI）= 1.23-23.69; P = 0.0096]和肿瘤复发的独立预测因子（风险比= 3.92; 95%置信区间= 1.11-25.14; P = 0.032）血清miR-1290是CRC早期检测、复发和预后的新生物标志物。
Our comprehensive miRNA microarray analyses identify the serum miRNA expression profiles differed significantly between controls and adenoma or CRC. Especially, miR-1290 expression is most statistically up-regulated in serum samples from adenoma or CRC patients versus controls, and is a promising, serum-based non-invasive biomarker for the detection and prognosis of colorectal neoplasia.Circulating microRNAs (miRNAs) are attracting major interest as potential non-invasive biomarkers for colorectal cancer (CRC). This study aimed to identify a novel serum miRNA biomarker for the early detection and/or evaluating prognosis of CRC patients.Comprehensive miRNA array analysis was carried out using serum samples from patients with colorectal neoplasia and healthy controls. Next, to verify whether the candidate miRNA possessed a secretory potential, we screened miRNA expression levels in culture medium from 2 CRC cell lines, followed by serum analysis from 12 stage IV CRC, 12 adenoma, and 12 control subjects. Thereafter, we validated expression of candidate miRNAs in 179 primary CRC tissues, as well as serum samples from an independent cohort of 211 CRCs, 56 adenomas, and 57 control subjects.Through microarray analysis, we identified significantly higher levels of miRNA-1290 (miR-1290) in serum from patients with colorectal adenomas and cancers. We verified miR-1290 overexpression in serum of CRC patients in a training cohort. In the validation cohort, serum miR-1290 levels were significantly up-regulated in patients with colorectal adenomas (P < 0.0001) and cancers (P < 0.0001). Serum miR-1290 levels could robustly distinguish adenoma [area under the curve (AUC) = 0.718] and CRC patients (AUC = 0.830) from normal subjects. High miR-1290 expression in serum and tissue was significantly associated with tumor aggressiveness and poor prognosis. Moreover, serum miR-1290 levels were an independent prognostic factor [hazard ratio (HR) = 4.51; 95% confidence interval (CI) = 1.23-23.69; P = 0.0096] and an independent predictor for tumor recurrence (hazard ratio = 3.92; 95% confidence interval = 1.11-25.14; P = 0.032) in CRC.Serum miR-1290 is a novel biomarker for early detection, recurrence, and prognosis in CRC.