Melanoma Spotlight: New Perspective Through Biophysical Markers

Melanoma is a highly aggressive skin cancer with strong metastatic potential, with the lung being one of the earliest and most frequent sites of dissemination. Considering the role of the tumor microenvironment in cancer progression, this study employs an integrated biophysical signature framework combining Raman spectroscopy (RS) and Atomic Force Microscopy (AFM) to characterize melanoma progression at biochemical and ultrastructural levels. Melanoma cell lines SK-MEL-19 and SK-MEL-103 were compared with MRC-5 lung fibroblasts to establish a graded model of tumor aggressiveness. Raman spectroscopy revealed distinct biochemical signatures in melanoma cells, including increased contributions from bands associated with amino acids, nucleic acids, lipids, and amide groups, reflecting metabolic reprogramming and biosynthetic activity, with a clear progression from fibroblasts to SK-MEL-19 and SK-MEL-103. AFM analysis revealed corresponding ultrastructural signatures characterized by progressive loss of cellular organization, increased nuclear irregularity, and membrane topographical alterations, particularly in SK-MEL-103 cells. Morphometric parameters, including nuclear and cytoplasmic volumes, nucleus-to-cytoplasm ratio, and relative surface area, supported a graded structural transition associated with tumor progression. The integration of Raman and AFM parameters defines a coherent biophysical signature framework capable of distinguishing non-tumor and melanoma phenotypes and resolving different stages of aggressiveness. SK-MEL-103 exhibited the most advanced malignant signature, while SK-MEL-19 showed intermediate characteristics. These findings highlight multimodal biophysical profiling as a robust approach for tumor characterization, linking biochemical remodeling to nanoscale structural reorganization in melanoma progression.