Insulin-like growth factor-I and prostate cancer: a meta-analysis

Some, but not all, epidemiological found have shown that high circulating levels of insulin-like growth factor-I (IGF-I) are associated with an increased risk of prostate cancer. We performed a meta-analysis on all the studies reported so far to evaluate this association. In our Medline search, 14 case–control studies were identified. A standard protocol abstracted information for each study. Hedges' standardized mean difference (HSMD) and odds ratio (OR) were used to estimate the effect of IGF-I and IGF-binding proteins (IGFBP-3). The combined data showed that circulating levels of IGF-I were significantly higher in prostate cancer patients (HSMD = 0.194). The OR for prostate cancer was 1.47 (95% confidence interval (CI) 1.23–1.77) among men with high IGF-I compared to those with low IGF-I. The OR was 1.26 (95% CI 1.03–1.54) for IGFBP-3. Circulating levels of IGF-I and IGFBP-3 are likely to be higher in prostate cancer patients than in the controls. These findings support the suggestion that high IGF-I and IGFBP-3 are associated with an increased risk of prostate cancer. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Reference miRNAs for miRNAome Analysis of Urothelial Carcinomas

Background/Objective: Reverse transcription quantitative real-time PCR (RT-qPCR) is widely used in microRNA (miRNA) expression studies on cancer. To compensate for the analytical variability produced by the multiple steps of the method, relative quantification of the measured miRNAs is required, which is based on normalization to endogenous reference genes. No study has been performed so far on reference miRNAs for normalization of miRNA expression in urothelial carcinoma. The aim of this study was to identify suitable reference miRNAs for miRNA expression studies by RT-qPCR in urothelial carcinoma. Methods: Candidate reference miRNAs were selected from 24 urothelial carcinoma and normal bladder tissue samples by miRNA microarrays. The usefulness of these candidate reference miRNAs together with the commonly for normalization purposes used small nuclear RNAs RNU6B, RNU48, and Z30 were thereafter validated by RT-qPCR in 58 tissue samples and analyzed by the algorithms geNorm, NormFinder, and BestKeeper. Principal Findings: Based on the miRNA microarray data, a total of 16 miRNAs were identified as putative reference genes. After validation by RT-qPCR, miR-101, miR-125a-5p, miR-148b, miR-151-5p, miR-181a, miR-181b, miR-29c, miR-324-3p, miR-424, miR-874, RNU6B, RNU48, and Z30 were used for geNorm, NormFinder, and BestKeeper analyses that gave different combinations of recommended reference genes for normalization. Conclusions: The present study provided the first systematic analysis for identifying suitable reference miRNAs for miRNA expression studies of urothelial carcinoma by RT-qPCR. Different combinations of reference genes resulted in reliable expression data for both strongly and less strongly altered miRNAs. Notably, RNU6B, which is the most frequently used reference gene for miRNA studies, gave inaccurate normalization. The combination of four (miR-101, miR-125a-5p, miR-148b, and miR-151-5p) or three (miR-148b, miR-181b, and miR-874,) reference miRNAs is recommended for normalization