A Single-Nucleotide Polymorphism In The 3 '-Utr Region Of The Adipocyte Fatty Acid Binding Protein 4 Gene Is Associated With Prognosis Of Triple Negative Breast Cancer

Objective Triple negative breast cancer (TNBC) is a subtype with poor prognosis and high heterogeneity. The aim of this study was to screen single nucleotide polymorphisms (SNPs) associated with the prognosis of TNBC patients and to explore the potential mechanism. Methods We selected SNPs(MAF≥1%) located on the 39 untranslated region (39UTR) of differentially expressed genes in breast cancer through databases (Nextbio,ensemble,NCBI,MirSNP). We investigated the possible associations between 111 SNPs and progression risk among 323 TNBC patients using two-step case-control study with discovery cohort (n=162) and validation cohort (n=161). The Benjamini Hochberg false discovery rate (FDR) method was used to assess the statistical significance after correction for multiple comparisons. Kaplan-Meier analysis was applied in order to assess the association between disease free survival (DFS) and positive SNPs, as well as Body Mass Index(BMI). We also investigated the expression of FABP4 in adipocytes adjacent to TNBC tissues (n=35) using immunohistochemistry. The integrated optical density (IOD) was measured as an approximation of FABP4 expression. Mann-Whitney U test was used in an attempt to assess the correlations among SNPs in FABP4, FABP4 expression and TNBC prognosis. Results SNPs in FABP4, KRAS and NTRK2 genes associated with the recurrence risk of TNBC throughout the discovery cohort and validation cohort, while the statistical significance was retained after multiple comparisons only for FABP4 rs1054135. The G allele of rs1057035 was associated with decreased risk of disease progression (aHR 0.14, 95%CI0.03-0.66), as well as an increased DFS (P Conclusions Our study found a lipid metabolism related gene and an important SNP in the 39UTR of FABP4 associated with TNBC prognosis, which may aid the screening of high-risk patients with TNBC recurrence and the development of novel chemotherapeutic agents. Citation Format: Yuan P, Wang W, Wu C, Lin D, Xu B. A single-nucleotide polymorphism in the 39-UTR region of the adipocyte fatty acid binding protein 4 gene is associated with prognosis of triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-19.