Raman imaging and chemometric methods in human normal bronchial and cancer lung cells: Raman biomarkers of lipid reprogramming

Abstract

This paper presents an approach to study biochemical changes in human normal bronchial cells (BEpiC) and human cancer lung cells (A549) by Raman spectroscopy and Raman imaging combined with chemometric methods. Based on Raman spectra and Raman imaging combined with chemometric methods we have proved that peaks at 845 cm^-1, 2845 cm^-1, 2936 cm^-1, 1444 cm^-1, 750 cm^-1, 1126 cm^-1, 1584 cm^-1, can be treated as Raman biomarkers probing phosphorylation, lipid reprogramming, oxidative phosphorylation and changes in cholesterol and cytochrome in normal and cancer cells. Raman analysis of the bands at 845 cm^-1, 2845 cm^-1, 1444 cm^-1, and 1126 cm^-1 in human cancer lung cells and human normal bronchial cells demonstrate enhanced phosphorylation and triglycerides de novo synthesis, reduced levels of cholesterol and cytochrome c in cancer cells. The sensitivity is equal to 100% (nucleus), 87.5% (mitochondria), 100% (endoplasmic reticulum), 87.5% (lipid droplets), 87.5% (cytoplasm), 87.5% (cell membrane) for A549 cell line and 83.3% (nucleus), 100% (mitochondria), 83.3% (endoplasmic reticulum), 100% (lipid droplets), 100% (cytoplasm), 83.3% (cell membrane) for BEpiC. The values of specificity for cross-validation equal 93.4% (nucleus), 85.5% (mitochondria), 89.5% (endoplasmic reticulum), 90.8% (lipid droplets), 61.8% (cytoplasm), 94.7% (cell membrane) for A549 cell line and 88.5% (nucleus), 85.9% (mitochondria), 85.9% (endoplasmic reticulum), 97.4% (lipid droplets), 75.6% (cytoplasm), 92.3% (cell membrane) for BEpiC. We have confirmed that Raman spectroscopy methods combined with PLS-DA are useful tools to monitor changes in human cancer lung cells and human normal bronchial cells.

Keywords: Biomarkers; Lung cancer; PLS-DA; Raman imaging; Raman spectroscopy.