title: 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.
abstract: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and high heterogeneity. The aim of this study was to screen patients for single-nucleotide polymorphisms (SNPs) associated with the prognosis of TNBC. Database-derived SNPs (NextBio, Ensembl, NCBI and MirSNP) located in the 3'-untranslated regions (3'-UTRs) of genes that are differentially expressed in breast cancer were selected. The possible associations between 111 SNPs and progression risk among 323 TNBC patients were investigated using a two-step case-control study with a discovery cohort (n=162) and a validation cohort (n=161). We identified the rs1054135 SNP in the adipocyte fatty acid binding protein 4 (FABP4) gene as a predictor of TNBC recurrence. The G allele of rs1054135 was associated with a reduced risk of disease progression as well as a prolonged disease-free survival time (DFS), with a hazard ratio (HR) for recurrence in the combined sample of 0.269 [95%CI: 0.098-0.735;P=0.001]. Notably, for individuals having the rs1054135 SNP with the AA/AG genotype, the magnitude of increased tumour recurrence risk for overweight patients (BMI≥25kg/m2) was significantly elevated (HR2.53; 95%CI: 1.06-6.03). Immunohistochemical staining of adipocytes adjacent to TNBC tissues showed that the expression level of FABP4 was statistically significantly lower in patients with the rs1054135-GG genotype and those in the disease-free group (P=0.0004 and P=0.0091, respectively). These results suggested that the expression of a lipid metabolism-related gene and an important SNP in the 3'-UTR of FABP4 are associated with TNBC prognosis, which may aid in the screening of high-risk patients with TNBC recurrence and the development of novel chemotherapeutic agents.
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China.|Phase I Clinical Trial Center, Beijing Shijitan Hospital, Capital Medical University, The 9th Clinical College, Beijing, P.R. China.
authors.forename: Wenmiao
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Du
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China.
authors.forename: Anjie
authors.initials: A
authors.lastname: Zhu
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China.
authors.forename: Pin
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, Cancer Institute and Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R. China.
authors.forename: Binghe
authors.initials: B
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions; D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D018572:Disease-Free Survival; D050556:Fatty Acid-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins
keywords: 3′-untranslated regions; FABP4; genetic variant; prognosis; triple-negative breast cancer