Identification of Gene Expression Profiles Associated With Different Types of Breast Adipose and Their Relationship to Tumorigenesis.

摘要

Purpose:Having long been thought to function only as aninert energy storage depot, the role of adipose tissue in tumorigenesis has been largely ignored. Improved understanding of the role of adipose in tumorigenesis is crucial given the increasing rates of obesity and the use of autologous fat transferin breast reconstruction. Scope: Adipose, adjacent to and distant from invasive breast tumors, was laser microdissected from 20 post-menopausal women, and from 20 post-menopausal women with nonmalignant breast disease. Gene expression data were generated using U133 2.0 microarrays. Data were analyzed to identify significant patterns of differential expression between adipose classes. Data were validated using qRT-PCR. Major findings:Immune response differs in a gradient fashion between non-malignant, distant and tumor adjacent adipose,with the largest response closest to the tumor. FCGR2A, FOLR2, LGMN, MARCO and NLRP3 were expressed at significantly higher levels and HLA-DQB1 and HLA-DQA1 at significantly lower levels in adipose from invasive breasts compared to non-malignant breasts. MMP9,PLA2G7, RRM2 and SPP1 were expressed at significantly higher levels inadjacent compared to distant adipose. Thus, adipose is not an inert component of the breast microenvironment but plays an active role in tumorigenesis.