Genomic and immunological characterization between primary and recurrent breast cancer.

Abstract

e12553 Background: A large number of breast cancer patients suffered cancer recurrence. Survival was seriously worse in recurred tumor. Immune microenvironment and pathways inducing drug resistance were closely related to tumor recurrence. It is necessary to clarify the recurrence mechanisms and improve recurrence detection. Methods: Somatic mutation, expression matrix and clinical information of primary (n = 1177) and recurred (n = 803) breast tumors in METABRIC were downloaded from cBioPortal. The Kaplan-Meier method of survival analysis was used to display overall survival. Significantly mutated genes (SMG) identified by MutSig2CV (v3.11) with Qvalue < 0.05. R packages CIBERSORT was applied to calculate the proportion of tumor-infiltrating immune cell using mRNA expression microarray data. Student's t-test was used to compare the SMGs expression log intensity levels of two groups. Results: Overall survival were significantly difference between the primary and recurred patients (log-rank test, P value < 0.0001). The immune cell components of primary and recurred breast tumors presented different patterns. Macrophages were significantly enriched in primary patients (Kruskal-Wallis test, P value < 0.05). PIK3R1, SMAD4, ATR and FLT3 were uniquely significantly mutated and expressed at lower levels in recurred group. These SMGs were identified as being associated with recurrence in other cancer studies. For example, PIK3R1 regulates the transduction of PI3K/Akt pathway, which disrupting the balance between induction and prevention of apoptosis, causing drug resistance. In the other, SMAD4 acts as a central mediator of TGF-β/SMAD4 signaling pathway that usually impedes immune cell activation. Conclusions: Recurred breast tumors presented different genetic mutation frequency and microenvironment. Tumor immune factors are associated with recurrence. Detecting uniquely SMGs of recurred breast tumors may be a feasibility way to monitor disease recurrence.