Evaluating HER2 amplification status and acquired drug resistance in breast cancer cells using Raman spectroscopy

Abstract

Abstract. The overexpression of human epidermal growth factor receptor 2 (HER2) is associated with increased breast cancer recurrence and worse prognosis. Effective treatments such as trastuzumab and lapatinib for patients with HER2 overexpression target the blockade of HER2 signaling activities but are often limited by the emergence of acquired drug resistance. This study applied Raman spectroscopy to differentially identify the amplification status of HER2 in cells and to characterize the biochemical composition of lapatinib resistant and sensitive HER2+ breast cancer cells in response to the drug. Raman spectra from BT474 (HER2+ breast cancer cell), MCF-10A (HER2− control), and HER2+ MCF-10A (HER2+ control) were analyzed using lasso and elastic-net regularized generalized linear models (glmnet) for multivariate statistical analysis and were discriminated to groups of different HER2 expression status with an overall 99% sensitivity and specificity. Enhanced lipid content and decreased proteome were observed in HER2+ cells. With lapatinib treatment, lapatinib-resistant breast cancer cells demonstrated sustained lipogenesis compared with the sensitive cells. © The Authors.Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

In vivo imaging of the tumor and its associated microenvironment using combined CARS / 2-photon microscopy

“…In the future, an exciting possibility is that the successes of Raman based techniques in identifying immune cell types, 36,37 differences between normal, benign and malignant tissues, 38-40 and the discrimination between drug sensitive and drug resistant tumors, 41 may be transferable to coherent Raman imaging by further developing and exploiting the spectroscopic data generated while imaging.…”

The Clinical Application of Raman Spectroscopy for Breast Cancer Detection

“…Hartsuiker et al reported variance in lipid levels among breast cancer cell lines with varying HER2 expression levels [13]. Bi et al used Raman spectroscopy to detect lipids in cell lines [48]. In the cell lines treated with lapatinib, a drug-targeting HER2, the lipid levels were increased in the drug-resistant cells.…”

“…Studies have shown that patients with HER2-positive breast cancer are at increased risks of recurrence and metastasis [47]. HER2 proto-oncogene expression can be detected by Raman spectra, which have also been used to detect HER2 expression in the BT474 (HER2+), MCF-10A (HER2−), and MCF-10A (HER2+) cell lines [48]. In this study, the application of Raman spectra was first used to characterize the biochemical response of drug resistance and sensitivity to lapatinib, a targeted antitumor agent.…”

Distinguishing Cancerous Liver Cells Using Surface-Enhanced Raman Spectroscopy

“…27,52 Many studies report the Raman spectroscopic detection of malignant and premalignant tissues in different sites of the body with high sensitivities, has the potential as a new tool in the clinico-oncological practice. 19 The diagnostic potential of Raman spectroscopy has been demonstrated in cancers of various organs including the esophagus, 53 breast, 54 lung, 55 bladder, 56 skin, 57 and prostate. 31 This work described the spectra investigation of single normal and cancerous liver cells using confocal Raman microspectroscopy technology.…”