Rachana Garg
Deapartment of Surgery, City of Hope Medical Center, California, USA
Title: CBX2: a potential marker of HER2+ breast-to-brain metastasis
Biography
Biography: Rachana Garg
Abstract
Breast cancer brain metastases (BBM) represent a significant clinical challenge, with patients having a dismal 20% one-year survival. In the present study, we investigated the differential gene expression profile between tumor and normal samples by querying various public breast cancer cohorts, including TCGA BRCA, METABRIC, GSE11121, GSE17705, GSE12276, and CCLE. We compared the mean threshold in the breast cancer population, specifically in the ER+/HER2+ and TNBC, the more aggressive breast cancer subtypes. We further compared the expression levels across PAM50 subtypes to obtain unambiguous conclusions. The Kaplan-Meier (KM) analysis was performed to correlate overall survival curves based on gene expression data using the median as a threshold from TCGA and METABRIC breast carcinoma cohorts. Importantly, analysis done using TCGA-BRCA revealed elevated CBX2 mRNAseq gene expression in breast tumors than in normal tissue. Additionally, CBX2 mRNA seq expression showed a pattern of TNBC > HER2+ >all tumor >ER+ > normal tissue. Using Novartis/Broad Cancer Cell Line Encyclopedia (CCLE) for microarray and RNAseq gene expression profiling, we identified enhanced CBX2 mRNA expression in breast cancer cell lines compared to other cancer types. CBX2 mRNAseq expression was significantly greater among HER2+ (n=164) compared to normal (n=112) patients (FC=4.9; p=8.19e-36) and TNBC (n=115; FC=11, p-value= 1.27e-6) from TCGA breast cancer cohort. Additionally, METABRIC cohorts also showed a significant correlation between higher CBX2 mRNA expression and poor overall survival outcome (Kaplan-Meier analysis, n=1904, p- value= 0.0001). Thus, our investigation has identified CBX2 as a potential driver of HER2+ breast-to-brain metastasis and inhibition of CBX2 should be considered as a therapeutic target in breast-to-brain metastasis.