A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis

• Published in: European journal of cancer (1990) 2011-03, Vol.47 (5), p.784-791
• Main Authors: Liu, Rui, Zhang, Chunni, Hu, Zhibin, Li, Gou, Wang, Cheng, Yang, Cuihua, Huang, Dingzhi, Chen, Xi, Zhang, Haiyang, Zhuang, Rui, Deng, Ting, Liu, Hua, Yin, Jingjing, Wang, Sufen, Zen, Ke, Ba, Yi, Zhang, Chen-Yu
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomarker; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; CA-19-9 Antigen - metabolism; Carcinoembryonic Antigen - metabolism; Case-Control Studies; Diagnosis; DNA Fingerprinting - methods; Female; Gastric cancer; Gene Expression Profiling - methods; Genome, Human - genetics; Hematology, Oncology and Palliative Medicine; Humans; Male; Medical sciences; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Pharmacology. Drug treatments; qRT-PCR; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; ROC Curve; Serum microRNA; Solexa; Stomach Neoplasms - diagnosis; Stomach Neoplasms - genetics; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2010.10.025

Abstract Background Prognosis of patients with gastric cancer (GC) is generally poor due to the lack of non-invasive tools for GC detection. The purpose of present study was to identify a serum microRNA (miRNA) expression profile that can serve as a novel diagnostic biomarker for GC detection and to assess its clinical applications in monitoring disease progression. Methods Serum samples were taken from 164 GC patients and 127 age- and gender-matched tumour-free controls. An initial screening of miRNA expression by Solexa sequencing was performed using serum samples pooled from 20 patients and 20 controls, respectively. Differential expression was validated using hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (qRT-PCR) in individuals samples, the samples were arranged in two phases. Results The Solexa sequencing results demonstrated that 19 serum miRNAs were markedly upregulated in the GC patients compared to the controls. The qRT-PCR analysis further identified a profile of five serum miRNAs (miR-1, miR-20a, miR-27a, miR-34 and miR-423-5p) as a biomarker for GC detection. The analysis results showed that the expression level of five serum miRNAs was correlated to tumour stage. The areas under the receiver operating characteristic (ROC) curve of this five-serum miRNA signature were 0.879 (95% confidence interval (CI) 0.822–0.936) and 0.831 (95% CI 0.767–0.898) for the two sets of serum samples, respectively, markedly higher than those of the biomarkers carcinoembryonic antigen (CEA) (0.503) and carbohydrate antigen 19-9 (CA19-9) (0.600). Conclusions We identified five-miRNA signature for GC diagnosis by genome-wide serum miRNA expression profiling. Expression levels of this serum miRNA-based biomarker also indicate tumour progression stages.