Heterogeneity characterization of breast cancer biopsies by metabolic profiling using HR MAS MRS analysis

Abstract

Summary Biotechnology Heterogeneity characterization of breast cancer biopsies by metabolic profiling using HR MAS MRS analysis KEYWORDS: Metaboloics, HR MAS MRS, breat cancer hetrogeneity, multivariate analysis, PCA Marina Perea Badia Angels Sierra, Guro F. Giskeødegård, Tone Frost Bathen Breast cancer is a heterogeneous disease with a varying pronogsis. Today’s clinical factors provide some information about prognosis of a breast cancer patient; however there is a need for additional information to stratify patients for improved and more individualized treatment. Breast tumors are highly heterogeneous due to subpopulations of cancer cells that differ in genetic and phenotypic characteristics. Tumor heterogeneity has been associated with treatment resistance and relapse. Additionally, it can be questioned how representatice one biopsy is for the whole tumor. Tumor phenotypic heterogeneity cannot be solely attributed to genetic differences, as epigenetics and interaction with the tumor microenviorment also contribute. The aim of this study was to examine intra-tumor and inter.tumor heterogeneity through metabolic profiling in breast cancer tissue. Fresh frozen tissue slices from the middle of surgically removed breast tumors were used. Five cores throughout the slices were drilled out from 10 tumors, of which six IDC grade 2-3 and four fibroadenomas. Histological examination of each core was performed by HE staining, and metabolic profiling of intact tissue samples were performed by high resolution magnetic angle spinning (HR MAS) magnetic resonance spectroscopy (MRS). The relative concentrations of 23 metabolites were quantified. Metabolic heterogeneity was measured by coefficient of variation (CoV) and multivariate PCA was used for explain metabolic variance. The study showed that patients diagnosed with high-grades of IDC had higher metabolic differences compared to patients diagnosed with fibroadenomas. No evidences were found for metabolic intratumor heterogeneity associated with sample location within the tumor. Breast tissue samples examinations by pathologist provide important information in order to characterize intratumor metabolic variations, highlighting the strong role of histology evaluation. Overall, MRS metabolomics contributed to a valuable tool for further characterization of tumor heterogeneity and for identifying opportunities for imporving stratification of patients into clinically useful diagnosed groups.