High-Throughput Metabolomic Profiling of Skin Lesions: Comparative Study of Cutaneous Squamous Cell Carcinoma, Basal...

Rising rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) make standard histopathology diagnostic methods a bottleneck. Using tissue molecular information for diagnostics offers a promising alternative. Faster specimen collection and high-throughput molecular identification can improve the processing of the increasing number of tumors. This study aims (i) to confirm the ability of e-biopsy technique to harvest metabolites, (ii) to obtain high-resolution metabolomic profiles of cSCC, BCC, and healthy skin tissues, and (iii) to perform a comparative analysis of the collected profiles.

Tumor specimens were collected with electroporation-based biopsy (e-biopsy), a minimally invasive sampling collection tool, from 13 tissue samples (cSCC, BCC, and healthy skin) from 12 patients. Ultra performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS) was used for molecular identification and quantification of resulting metabolomic profiles.

Here we report measurements of 2325 small metabolites identified (301 with high confidence) in 13 tissue samples from 12 patients. Comparative analysis identified 34 significantly (p < 0.05) differentially expressed high-confidence metabolites. Generally, we observed a greater number of metabolites with higher expression, in cSCC and in BCC compared to healthy tissues, belonging to the subclass amino acids, peptides, and analogues.

These findings confirm the ability of e-biopsy technique to obtain high-resolution metabolomic profiles suitable to downstream bioinformatics analysis. This highlights the potential of e-biopsy coupled with UPLC-MS-MS for rapid, high-throughput metabolomic profiling in skin cancers and supports its utility as a promising diagnostic alternative to standard histopathology.

The online version contains supplementary material available at 10.1007/s12195-025-00846-1.