Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie.
Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie
Ann Oncol. 2016 Oct;27(10):1879-86. doi: 10.1093/annonc/mdw279. Epub 2016 Aug 8.
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.
循环 microRNAs（miRNAs）作为结直肠癌（CRC）的潜在非侵入性生物标志物引起了广泛关注。本研究旨在确定一种新型血清 miRNA 生物标志物，用于 CRC 患者的早期检测和/或评估预后。
使用结直肠肿瘤患者和健康对照者的血清样本进行全面 miRNA 阵列分析。接下来，为了验证候选 miRNA 是否具有分泌潜能，我们筛选了 2 种 CRC 细胞系培养基中的 miRNA 表达水平，然后对 12 例 IV 期 CRC、12 例腺瘤和 12 例对照者的血清进行了分析。此后，我们在 179 例原发性 CRC 组织以及 211 例 CRC、56 例腺瘤和 57 例对照者的独立队列血清样本中验证了候选 miRNA 的表达。
通过微阵列分析，我们发现血清中 miRNA-1290（miR-1290）在结直肠腺瘤和癌症患者中显著升高。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，结直肠腺瘤患者（P < 0.0001）和癌症患者（P < 0.0001）血清 miR-1290 水平显著上调。血清 miR-1290 水平可有效区分腺瘤（AUC = 0.718）和 CRC 患者（AUC = 0.830）与正常人群。血清和组织中高表达 miR-1290 与肿瘤侵袭性和不良预后显著相关。此外，血清 miR-1290 水平是 CRC 的独立预后因素[危险比（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（危险比= 3.92；95%置信区间= 1.11-25.14；P = 0.032）。
血清 miR-1290 是 CRC 早期检测、复发和预后的新型生物标志物。
