Dataset Information

Effects of soy supplementation on gene expression in breast cancer

ABSTRACT: Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomized to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString inin pre- and post-treatment tumor tissue. Genome-wide expression analysis was performed on post-treatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes (out of 202) showed altered expression (two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2 fold) of cell cycle transcripts, including those which promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein define a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer. Genome-wide expression analysis was performed on breast cancer tissue from women following treatment with soy (n=28) or placebo (n=23).

ORGANISM(S): Homo sapiens

SUBMITTER: Doane Ashley

PROVIDER: S-ECPF-GEOD-58792 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomized to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString inin pre- and post-treatment tumor tissue. Genome-wide expression analysis was performed on post-treatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes (out of 202) showed altered expression (two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2 fold) of cell cycle transcripts, including those which promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein define a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer. Genome-wide expression analysis was performed on breast cancer tissue from women following treatment with soy (n=28) or placebo (n=23).

Project description:Background: Breast cancer patients present lower 1,25(OH)2D3 or 25(OH)D3 serum levels than unaffected women. Although 1,25(OH)2D3 pharmacological concentrations of 1,25(OH)2D3 may exert antiproliferative effects in breast cancer cell lines, much uncertainty remains about the effects of calcitriol supplementation in tumor specimens in vivo. We have evaluated tumor dimension (ultrassonography), proliferative index (Ki67 expression), 25(OH)D3 serum concentration and gene expression profile, before and after a short term calcitriol supplementation (dose to prevent osteoporosis) to post-menopausal patients. Results: Thirty three patients with operable disease had tumor samples evaluated. Most of them (87.5%) presented 25(OH)D3 insufficiency (<30 ng/mL). Median period of calcitriol supplementation was 30 days. Although tumor dimension did not vary, Ki67 immunoexpression decreased after supplementation. Transcriptional analysis of 15 matched pre/post-supplementation samples using U133 Plus 2.0 GeneChip (Affymetrix) revealed 18 genes over-expressed in post-supplementation tumors. As a technical validation procedure, expression of four genes was also determined by RT-qPCR and a direct correlation was observed between both methods (microarray vs PCR). To further explore the effects of near physiological concentrations of calcitriol on breast cancer samples, an ex vivo model of fresh tumor slices was utilized. Tumor samples from another 12 post-menopausal patients were sliced and treated in vitro with slightly high concentrations of calcitriol (0.5nM), that can be attained in vivo, for 24 hours In this model, expression of PBEF1, EGR1, ATF3, FOS and RGS1 was not induced after a short exposure to calcitriol. Conclusions: In our work, most post-menopausal breast cancer patients presented at least 25(OH)D3 insufficiency. In these patients, a short period of calcitriol supplementation may prevent tumor growth and reduce Ki67 expression, probably associated with discrete transcriptional changes. This observation deserves further investigation to better clarify calcitriol effects in tumor behavior under physiological conditions. Post-menopausal patients with early stage breast cancer, in the absence of distant metastasis, were invited to take part in the study. This protocol was approved by the Institutional Ethics Committee, and a written informed consent was signed by all participants. Patients had blood and tumor samples collected during biopsy, and were prescribed calcitriol supplementation, (Rocaltrol)TM 0.50 μg/day PO, as recommended for osteoporosis prevention. Tumor specimens obtained during biopsy (pre-supplementation) or breast surgery (post-supplementation) were hand dissected and samples with at least 70% tumor cells were further processed. Breast surgery followed in about one month

Dataset Information

Effects of soy supplementation on gene expression in breast cancer

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets