Identification of a circulating microRNA signature for colorectal cancer detection.
Prognosis of patients with colorectal cancer (CRC) is generally poor because of the lack of simple, convenient, and noninvasive tools for CRC detection at the early stage. The discovery of microRNAs (miRNAs) and their different expression profiles among different kinds of diseases has opened a new avenue for tumor diagnosis. We built a serum microRNA expression profile signature and tested its specificity and sensitivity as a biomarker in the diagnosis of CRC. We also studied its possible role in monitoring the progression of CRC. We conducted a two phase case-control test to identify serum miRNAs as biomarkers for CRC diagnosis. Using quantitative reverse transcription polymerase chain reactions, we tested ten candidate miRNAs in a training set (30 CRCs vs 30 controls). Risk score analysis was used to evaluate the diagnostic value of the serum miRNA profiling system. Other independent samples, including 83 CRCs and 59 controls, were used to validate the diagnostic model. In the training set, six serum miRNAs (miR-21, let-7g, miR-31, miR-92a, miR-181b, and miR-203) had significantly different expression levels between the CRCs and healthy controls. Risk score analysis demonstrated that the six-miRNA-based biomarker signature had high sensitivity and specificity for distinguishing the CRC samples from cancer-free controls. The areas under the receiver operating characteristic (ROC) curve of the six-miRNA signature profiles were 0.900 and 0.923 for the two sets of serum samples, respectively. However, for the same serum samples, the areas under the ROC curve used by the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were only 0.649 and 0.598, respectively. The expression levels of the six serum miRNAs were also correlated with CRC progression. Thus, the identified six-miRNA signature can be used as a noninvasive biomarker for the diagnosis of CRC, with relatively high sensitivity and specificity.
Department of Etiology and Carcinogenesis, State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jia
J
Wang
Department of Etiology and Carcinogenesis, State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Sheng-kai
SK
Huang
Department of Etiology and Carcinogenesis, State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Mei
M
Zhao
Department of Etiology and Carcinogenesis, State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Mei
M
Yang
Department of Etiology and Carcinogenesis, State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jia-ling
JL
Zhong
Department of Etiology and Carcinogenesis, State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yu-yu
YY
Gu
Department of Etiology and Carcinogenesis, State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Hua
H
Peng
Department of Clinical Laboratory, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Yi-qun
YQ
Che
Department of Etiology and Carcinogenesis, State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Chang-zhi
CZ
Huang
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D008954:Models, Biological; D012334:RNA, Neoplasm / Q000097:blood*
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012334:RNA, Neoplasm