# Morphological and Optical Characterization of NRAS‐Mutant Melanoma Cells and Primary Melanocytes via Quantitative Phase Imaging With Digital Holographic Microscopy

## TL;DR

This study uses holographic microscopy to identify differences between normal skin cells and melanoma cells with NRAS mutations, offering a new tool for early cancer detection.

## Contribution

The study introduces a label-free method using digital holographic microscopy and data analysis to distinguish NRAS-mutant melanoma cells from normal melanocytes.

## Key findings

- Distinct morphological and optical differences were found between NRAS-mutant melanoma cells and melanocytes.
- Optical properties emerged as key features separating the two cell types.
- QPI with DHM shows potential as a non-invasive diagnostic tool for melanoma.

## Abstract

Early detection of melanoma, a highly variable and aggressive form of skin cancer, is crucial for improving patient outcomes. It is essential to distinguish malignant cells from normal melanocytes, and therefore, label‐free imaging methods that can do so are needed. Given the genotoxic effect of UV radiation, these mutations are numerous and affect many genes, including NRAS; therefore, therapeutic strategies can be directed toward these recurrent mutations. The aggressive nature of NRAS‐mutant melanoma contributes to poor patient prognosis, highlighting the need for early diagnosis. This study utilizes quantitative phase imaging (QPI) with digital holographic microscopy (DHM) to differentiate the morphology of NRAS‐mutant SK‐MEL‐2 cells from melanocytes using holographic microscopy; dimensionality reduction techniques, including Principal Component Analysis (PCA),t‐distributed stochastic neighbor embedding (t‐SNE); and clustering techniques, including K‐Means Elbow Plots and Hierarchical Clustering Dendrograms. The results demonstrated distinct morphologies and geometries between melanocytes and SK‐MEL‐2 cells, indicating that QPI with DHM can serve as a label‐free tool for identifying optical biomarkers in melanoma.

Melanoma is a deadly skin cancer that can be difficult to distinguish from normal pigment‐producing cells. This study uses digital holographic microscopy and advanced data analysis to uncover specific morphological and optical differences between healthy melanocytes and NRAS‐mutant melanoma cells. Our findings reveal that optical properties are among the most important features separating the two cell types. These results highlight the potential of holographic microscopy as a label‐free diagnostic tool and provide a foundation for developing new biomarkers to improve early detection of NRAS‐driven melanoma.