Evaluating HER2 amplification status and acquired drug resistance in breast cancer cells using Raman spectroscopy.
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.
Vanderbilt University, Department of Biomedical Engineering, VU Station B #351631, 2301 Vanderbilt Place, Nashville, Tennessee 37235bUniversity of Texas Health Science Center at Houston, Department of Nanomedicine and Biomedical Engineering, CABIR 3SCR.46.
Xiaohong
X
Bi
Vanderbilt University, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232.
Brent
B
Rexer
Vanderbilt University, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232.
Carlos L
CL
Arteaga
Vanderbilt University, Vanderbilt Center for Quantitative Sciences, Nashville, Tennessee 37232.
Mingsheng
M
Guo
Vanderbilt University, Department of Biomedical Engineering, VU Station B #351631, 2301 Vanderbilt Place, Nashville, Tennessee 37235.
Anita
A
Mahadevan-Jansen
D001943:Breast Neoplasms / Q000737:chemistry* / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013059:Spectrum Analysis, Raman / Q000379:methods*
D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human