In:
Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 23, No. 2 ( 2014-02-01), p. 288-299
Abstract:
Background: The development and progression of true interval breast cancers (tumors that truly appear after a negative screening mammogram) is known to be different from screen-detected cancers. However, the worse clinical behavior of true interval cancers is not fully understood from a biologic basis. We described the differential patterns of gene expression through microarray analysis in true interval and screen-detected cancers. Methods: An unsupervised exploratory gene expression profile analysis was performed on 10 samples (true interval cancers = 5; screen-detected cancers = 5) using Affymetrix Human Gene 1.0ST arrays and interpreted by Ingenuity Pathway Analysis. Differential expression of selected genes was confirmed in a validation series of 91 tumors (n = 12; n = 79) by immunohistochemistry and in 24 tumors (n = 8; n = 16) by reverse transcription quantitative PCR (RT-qPCR), in true interval and screen-detected cancers, respectively. Results: Exploratory gene expression analysis identified 1,060 differentially expressed genes (unadjusted P & lt; 0.05) between study groups. On the basis of biologic implications, four genes were further validated: ceruloplasmin (CP) and ribosomal protein S6 kinase, 70 kDa, polypeptide 2 (RPS6KB2), both upregulated in true interval cancers; and phosphatase and tensin homolog (PTEN) and transforming growth factor beta receptor III (TGFBR3), downregulated in true interval cancers. Their differential expression was confirmed by RT-qPCR and immunohistochemistry, consistent with mTOR pathway overexpression in true interval cancers. Conclusions: True interval and screen-detected cancers show differential expression profile both at gene and protein levels. The mTOR signaling is significantly upregulated in true interval cancers, suggesting this pathway may mediate their aggressiveness. Impact: Linking epidemiologic factors and mTOR activation may be the basis for future personalized screening strategies in women at risk of true interval cancers. Cancer Epidemiol Biomarkers Prev; 23(2); 288–99. ©2013 AACR.
Type of Medium:
Online Resource
ISSN:
1055-9965
,
1538-7755
DOI:
10.1158/1055-9965.EPI-13-0761
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036781-8
detail.hit.zdb_id:
1153420-5
