(296) UCKL1 is Dysregulated in the Transition from Early- to Late-Stage Breast Cancer in Younger Patients

Objective : The Incidence rate of breast cancer (BrCA) among very young adults is becoming an object of public concern in South Korea and elsewhere.These studies were designed to elucidate molecular pathways altered in the transition from early- to advanced-stage BrCA in young patients.

Methods: RNASeq data from a group of 50 young South Korean participants, 35 years-old or younger, with either early- or late-stage tumors was leveraged from the International Cancer Genome Consortium. Differentially expressed genes (DEGs) between these two groups were identified using Bioconductor’s DESeq2. The DEGs were subjected to pathway over-representation analysis. This was followed by Gene Set Enrichment Analyses (GSEA) using the Molecular Signatures Database (MSigDB). Similarly, identification of DEGs for BrCA data from the Cancer Genome Atlas (TCGA) involving young and mid-aged patients was performed. Moreover, both Korean and TCGA BrCA datasets were characterized by molecular subtypes.

Results: The over-represented pathways among the DEGs (p <.03) are: i) Platelet pathways, ii) Gamma-aminobutyric Acid Receptor Life Cycle pathway, iii) Fibrinolysis and Glucuronidation pathway over-represented. GSEA analysis showed that Vitamin D receptor pathway genes are enriched in early-stage tumors. UCKL1 is differentially expressed in early stage in both young BrCA Korean and young TCGA groups, even though the Korean cohort had more Basal-like BrCA

Conclusions: In very young women with BrCA in Korea, more advanced-stage tumors showed dysregulation in Platelet, Drug Metabolism, and Vitamin D Receptor Pathways. The Basal-like subtype is dominant among Korean participants and Luminal type is more dominant among the mostly white TCGA participants. UCKL1 might be an important gene in the transition from early- to late-stage in BrCA in younger patients.