PDF file - 73K, Association of miRNA expression at BL with response. Legend: This table reports the three miRNAs (miR-34c, miR-224, miR-375) that are significantly differentially expressed at BL in responders as compared to non-responders in at least one comparison The table shows up- or down-regulation in responders compared to non-responders. The significant p-values from Welch's t-test are reported. "FDR" indicates that the p-value is significant after adjustment for False Discovery Rate (FDR). Odds ratios (OR) were calculated by logistic regression model and reported with their 95% confidence interval and p-value. When either the t-test or the OR was significant, both are reported.
ARTICLE ABSTRACT
Lung cancers express lower levels of prostacyclin than normal lung tissues. Prostacyclin prevents lung cancer in a variety of mouse models. A randomized phase II trial comparing oral iloprost (a prostacyclin analog) with placebo in high-risk subjects showed improvement in bronchial histology in former, but not current, smokers. This placebo-controlled study offered the opportunity for investigation of other potential intermediate endpoint and predictive biomarkers to incorporate into chemoprevention trials.Matched bronchial biopsies were obtained at baseline and at 6-month follow-up from 125 high-risk individuals who completed the trial: 31/29 and 37/28 current/former smokers in the iloprost and placebo arm, respectively. We analyzed the expression of 14 selected miRNAs by Real Time PCR in 496 biopsies.The expression of seven miRNAs was significantly correlated with histology at baseline. The expression of miR-34c was inversely correlated with histology at baseline (P < 0.0001) and with change in histology at follow-up (P = 0.0003), independent of treatment or smoking status. Several miRNAs were also found to be differentially expressed in current smokers as compared with former smokers. In current smokers, miR-375 was upregulated at baseline (P < 0.0001) and downregulated after treatment with iloprost (P = 0.0023). No miRNA at baseline reliably predicted a response to iloprost.No biomarker predictive of response to iloprost was found. MiR-34c was inversely correlated with baseline histology and with histology changes. Mir-34c changes at follow-up could be used as a quantitative biomarker that parallels histologic response in formalin-fixed bronchial biopsies in future lung cancer chemoprevention studies. Cancer Prev Res; 6(2); 100–8. ©2012 AACR.
