Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer

被引:132
|
作者
Imaoka, H. [1 ]
Toiyama, Y. [1 ]
Fujikawa, H. [1 ]
Hiro, J. [1 ]
Saigusa, S. [1 ]
Tanaka, K. [1 ]
Inoue, Y. [1 ]
Mohri, Y. [1 ]
Mori, T. [2 ]
Kato, T. [3 ]
Toden, S. [4 ,5 ,6 ]
Goel, A. [4 ,5 ,6 ]
Kusunoki, M. [1 ]
机构
[1] Mie Univ, Grad Sch Med, Dept Gastrointestinal & Pediat Surg, 2-174 Edobashi, Tsu, Mie 5148507, Japan
[2] Moriei Hosp, Surg, Kuwana City, Japan
[3] Tohyama Hosp, Surg, Tsu, Mie, Japan
[4] Baylor Univ, Med Ctr, Ctr Gastrointestinal Res, Dallas, TX USA
[5] Baylor Univ, Med Ctr, Baylor Res Inst, Ctr Epigenet Canc Prevent & Canc Genom, Dallas, TX USA
[6] Baylor Univ, Med Ctr, Charles A Sammons Canc Ctr, Dallas, TX USA
关键词
serum; miR-1290; colorectal adenoma; colorectal cancer; diagnosis; prognosis; PROLIFERATION; MIR-1290; CELLS;
D O I
10.1093/annonc/mdw279
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1879 / 1886
页数:8
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