Breast cancer subtype specific biochemical responses to radiation

Abstract

External beam radiotherapy is a common form of treatment for breast cancer. Among patients and across different breast cancer subtypes, the response to radiation is heterogeneous. Radiation-induced biochemical changes were examined by Raman spectroscopy using cell lines that represent a spectrum of human breast cancer. Principal component analysis (PCA) and partial least squares discriminant analysis (PLSDA) revealed unique Raman spectral features in the HER2 and Ki67 subtype. The changes in Raman spectral profiles to different doses of radiation (0-50 Gy) included variations in the levels of proteins, lipids, nucleic acids and glycogen. Importantly, the differences in radiation-induced changes on the normal breast epithelial cell line MCF10A could be discriminated within and across the various breast tumor cell lines. These results demonstrate a novel approach to uncover differences between breast cancer cell subtypes and surrounding normal tissues by their biochemical variations in response to radiation.

Monitor Ionizing Radiation-Induced Cellular Responses with Raman Spectroscopy, Non-Negative Matrix Factorization, and Non-Negative Least Squares

“…Major peaks of glycogen at 482, 940, 1042, 1083, 1127, and 1385 cm −1 are present in the glycogen-like basis. 35 The lipid peak designation result is summarized in Table II. The majority of molecular assignment of Raman peaks were completed based on RS literature of lipids 36,37 and biological molecular constituents in cells.…”

Detection of acquired radioresistance in breast cancer cell lines using Raman spectroscopy and machine learning

“…[39][40][41][42] One particular study examined biochemical changes induced by radiation in an array of breast cancer cells using RS and multivariate analysis, it described changes in Raman profiles that show subtype-specific response to radiation. 43 A recent study utilised surface enhanced Raman spectroscopy (SERS) using gold nanoparticles to improve Raman signals and was able to clearly discriminate between radiosensitive and radioresistant murine lymphoma cells by significantly enhancing subtle chemical differences between the two sublines. 44 Fewer studies have applied RS to examine long-term radiationinduced biochemical changes in cells or tissue.…”

“…One study that utilised RS in acquired radioresistant oral cancer phenotypes, described changes in proteins and nucleic acids, possibly due to alterations of the cell signalling cascades induced by radiation. 45 A number of studies have looked at the immediate effects of radiation to cells and tissue of different cancers, [40][41][42][43]45,46 but none has so-far characterised long-term acquired radioresistance in breast cancer using RS; no study has yet described similar spectral differences after the development of acquired radioresistance with 100% accuracy in an array of both HR+ and HR-breast cancer cell lines.…”

Multivariate Analysis of Difference Raman Spectra of the Irradiated Nucleus and Cytoplasm Region of SH-SY5Y Human Neuroblastoma Cells

“…μ-RS has been employed to study the effects on cells induced by the γ-ray exposition and, above all, by the X-ray radiation at various doses for tumor and non-tumorigenic cell lines (see [17,18,19,20] and references therein). In particular, relevant radiobiological issues, such as the variation in patient radiosensitivity [18,21], the monitoring of patient’s radioresponse during the course of an extended treatment [22,23], and the failure of current models to predict cell survival at single high doses [17,18,21,24] have benefited from the contribution offered by μ-RS. In addition, it has been demonstrated to be useful also for investigating the radioresponse of various subtypes of breast cancers [22].…”

“…In particular, relevant radiobiological issues, such as the variation in patient radiosensitivity [18,21], the monitoring of patient’s radioresponse during the course of an extended treatment [22,23], and the failure of current models to predict cell survival at single high doses [17,18,21,24] have benefited from the contribution offered by μ-RS. In addition, it has been demonstrated to be useful also for investigating the radioresponse of various subtypes of breast cancers [22]. This technique has been also recently adopted to evaluate the radiobiological sensitivity of normal human breast cells to proton irradiation [25,26].…”