Abstract

Simple SummaryAlthough 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.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.

Highlights

  • Breast cancer is by far the most frequent cancer diagnosed in women, with 2,088,849 new cases (11.6% of total diagnosed cancer) accounting for 626,679 deaths (6.6%) in 2018 [1].the number of cancer survivors has been rapidly increasing due to improvements in early diagnosis and treatment efficacy [2,3,4]

  • For the first time, the spatial distribution of several molecular components (DNA, lipids, proteins, cytochrome C and polysaccharides) in the HAp calcifications extracted from a tumor microenvironment

  • In this paper we have presented a methodology that is capable of investigating the biochemical composition of HAp calcifications in human breast cancer tissue

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Summary

Introduction

The number of cancer survivors has been rapidly increasing due to improvements in early diagnosis and treatment efficacy (i.e., from 1989 to 2015, breast cancer death rates decreased by 39% in the US) [2,3,4]. Despite this positive trend, more efforts are needed to improve the basic understanding of the disease and the underlying cellular mechanisms in order to prevent its consequences. Thanks to the introduction of mammographic screening programs, the early diagnosis of breast cancer has substantially improved during recent years, enabling the detection of lesions at a much earlier stage.

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