Volatile metabolomic signature of human breast cancer cell lines

Abstract

Breast cancer (BC) remains the most prevalent oncologic pathology in women, causing huge psychological, economic and social impacts on our society. Currently, the available diagnostic tools have limited sensitivity and specificity. Metabolome analysis has emerged as a powerful tool for obtaining information about the biological processes that occur in organisms, and is a useful platform for discovering new biomarkers or make disease diagnosis using different biofluids. Volatile organic compounds (VOCs) from the headspace of cultured BC cells and normal human mammary epithelial cells, were collected by headspace solid-phase microextraction (HS-SPME) and analyzed by gas chromatography combined with mass spectrometry (GC-MS), thus defining a volatile metabolomic signature. 2-Pentanone, 2-heptanone, 3-methyl-3-buten-1-ol, ethyl acetate, ethyl propanoate and 2-methyl butanoate were detected only in cultured BC cell lines. Multivariate statistical methods were used to verify the volatomic differences between BC cell lines and normal cells in order to find a set of specific VOCs that could be associated with BC, providing comprehensive insight into VOCs as potential cancer biomarkers. The establishment of the volatile fingerprint of BC cell lines presents a powerful approach to find endogenous VOCs that could be used to improve the BC diagnostic tools and explore the associated metabolomic pathways.

Figure 1. Formation of some intermediate products of lipid peroxidation.

Adapted from ref. .

Figure 2. Distribution of VOCs identified in cultured breast cell lines.

Figure 3. Distribution by chemical families of VOCs identified in culture media at different pH conditions of breast cell lines.

Figure 4

(A) Separation of breast cancer cell lines and normal cells based on PCA scores scatter plot and (B) Line plot of principal component values obtained using selected compounds by significance of one-way ANOVA (p < 0.05) obtained from the analysis of 4 types of breast cell lines.

Figure 5

(A) Partial Least Square Analysis (PLS) scatter plot and (B) Line plot of selected compounds by significance of one-way ANOVA (p < 0.05) obtained from the analysis of 4 types of breast cell lines using cultured headspace analysis.

Figure 6

(A) Linear discriminant analysis (LDA) scatter plot of cultured headspace from breast cell samples (B) Classification of breast cells according to the canonical discriminant functions. Legend: BL-breast luminal; N- normal; BTN- breast triple negative.