Differential gene expression in preoperative study of selenium and vitamin E chemoprevention in prostate cancer

Abstract

1523 Background: To identify genes that distinguish between treatments, tumor types, and their interaction, we undertook a microarray analysis of tissue in a preoperative chemoprevention study of L-selenomethionine (SeMet) and vitamin E (VE) in prostate cancer. Methods: Forty-eight men with prostate cancer were enrolled in a single-institution, double-blind, placebo-controlled trial that randomized patients into four groups receiving 200 μg SeMet, 400 IU VE, a combination of the two, or placebo (see 2006 ASCO abstract 1007). All patients also received a multivitamin and vitamin C (250 mg) daily. Modeled on the Selenium and Vitamin E Cancer Prevention Trial, this study included patients scheduled for prostatectomy within 3 to 6 wk of registration who had a prostate-specific antigen level <10 ng/mL within 3 mo of registration, clinical stage T1c/T2 disease, and a Gleason score =7. From core biopsy specimens, we isolated cancerous and noncancerous cells, tumor-adjacent stroma, and non-tumor adjacent stroma of 38 evaluable radical prostatectomy specimens using laser capture microdissection. The cDNA hybridized to oligonucleotide microarrays was generated from extracted RNA, which had undergone two rounds of linear amplification. Expression levels were extracted using the positional-dependent nearest-neighbor model, and after ANOVA model analysis, effects were contrasted using the approximate z-test with statistic z. The beta-uniform mixture model was used to analyze p values and control the false discovery rate. Ingenuity Pathway Analysis followed. Results: Differentially expressed genes were selected that were common in the combination and selenium arms or in the combination and VE arms: unique in tumor-69 in combination and selenium, 71 in combination and VE; unique in stroma-64 in combination and selenium, 45 in combination and VE; unique in normal tissue-48 in combination and selenium, 38 in combination and VE. Conclusions: This work demonstrates that gene expression may be correlated with specific therapeutic interventions, and this analysis indicates that dietary antioxidants modulate gene expression in human prostate cancer cells and pathways relevant to prostate carcinogenesis. No significant financial relationships to disclose.