Journal
CLINICAL CANCER RESEARCH
Volume 21, Issue 5, Pages 1225-1233Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-14-1761
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Funding
- National Natural Science Foundation of China [81301506, 81300297, 81271916]
- Research Fund for the Doctoral Program of Higher Education of China [20130131120067]
- Shandong Province Natural Science Foundation [ZR2013HQ063]
- Shandong Technological Development Project (STDP) [2013GSF11859]
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Purpose: Cell-free Bmi-1 mRNA is stably detectable in the serum/plasma and is associated with the development and progression of some tumors. Previous methods detecting extracellular Bmi-1 mRNA with RNA extraction are inefficient. This study developed a novel reverse transcription quantitative PCR (RT-qPCR) approach directly applied in serum (RT-qPCR-D) to quantify Bmi-1 mRNA, and assessed its diagnostic and prognostic potential in colorectal cancer. Experimental Design: The feasibility of the RT-qPCR-D method was first analyzed in 50 serum samples. Then, using the RT-qPCR-D method, Bmi-1 mRNA expression was validated in serum from an independent cohort of patients with 87 normal colonoscopy, 76 hyperplastic polyp, 82 inflammatory bowel disease, 68 adenoma, and 158 colorectal cancer. Receiver operating characteristic (ROC) curves and Cox analyses were used to evaluate its diagnosis and prognosis value, respectively. Results: In a pilot study, levels of Bmi-1 mRNA were increased in colorectal cancer serum samples detected by RT-qPCR-D and significantly associated with results obtained by RT-qPCR. In a validation cohort, serum Bmi-1 mRNA levels were significantly elevated in the colorectal cancer group and the adenoma group when compared with other groups. The area under ROC curve distinguishing colorectal cancer from benign colorectal diseases was 0.888, with 72.2% sensitivity and 94.9% specificity, which was superior to carcinoembryogenic antigen. Bmi-1 mRNA levels were significantly associated with survival. Cox analysis indicated Bmi-1 mRNA was an independent prognostic factor for overall survival. Conclusions: Detection of cell-free Bmi-1 mRNA in serum by RT-qPCR-D is a simple and noninvasive approach and may be used for colorectal cancer diagnosis and prognosis. (C) 2014 AACR.
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