Unravelling the Encapsulation of DNA and Other Biomolecules in HAp Microcalcifications of Human Breast Cancer Tissues by Raman Imaging

SIMPLE SUMMARY: Although microcalcifications can be considered one of the first indicators of suspicious cancer lesions, depending on their morphology and distribution, the formation of hydroxyapatite calcifications and their relationship with malignancy remains unknown. In this work, we investigate in depth the biochemical composition of breast cancer microcalcifications, combining Raman spectroscopy imaging and advanced multivariate analysis. We demonstrate that DNA is naturally adsorbed and encapsulated inside hydroxyapatite found in breast cancer tissue. Furthermore, we also show the encapsulation of other relevant biomolecules such as lipids, proteins, cytochrome C and polysaccharides. The demonstration of the natural DNA biomineralization in cancer tissues represents an unprecedented advance in the field, as it can pave the way to understanding the role of hydroxyapatite in malignant tissues. ABSTRACT: Microcalcifications are detected through mammography screening and, depending on their morphology and distribution (BI-RADS classification), they can be considered one of the first indicators of suspicious cancer lesions. However, the formation of hydroxyapatite (HAp) calcifications and their relationship with malignancy remains unknown. In this work, we report the most detailed three-dimensional biochemical analysis of breast cancer microcalcifications to date, combining 3D Raman spectroscopy imaging and advanced multivariate analysis in order to investigate in depth the molecular composition of HAp calcifications found in 26 breast cancer tissue biopsies. We demonstrate that DNA has been naturally adsorbed and encapsulated inside HAp microcalcifications. Furthermore, we also show the encapsulation of other relevant biomolecules in HAp calcifications, such as lipids, proteins, cytochrome C and polysaccharides. The demonstration of natural DNA biomineralization, particularly in the tumor microenvironment, represents an unprecedented advance in the field, as it can pave the way to understanding the role of HAp in malignant tissues.