High-throughput lipidomic profiles sampled with electroporation-based biopsy differentiate healthy skin, cutaneous squamous cell carcinoma, and basal cell carcinoma

Abstract

Background: The incidence rates of cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) skin cancers are rising, while the current diagnostic process is time-consuming. We describe the development of a novel approach to high-throughput sampling of tissue lipids using electroporation-based biopsy, termed e-biopsy. We report on the ability of the e-biopsy technique to harvest large amounts of lipids from human skin samples.

Materials and methods: Here, 168 lipids were reliably identified from 12 patients providing a total of 13 samples. The extracted lipids were profiled with ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS) providing cSCC, BCC, and healthy skin lipidomic profiles.

Results: Comparative analysis identified 27 differentially expressed lipids (p < 0.05). The general profile trend is low diglycerides in both cSCC and BCC, high phospholipids in BCC, and high lyso-phospholipids in cSCC compared to healthy skin tissue samples.

Conclusion: The results contribute to the growing body of knowledge that can potentially lead to novel insights into these skin cancers and demonstrate the potential of the e-biopsy technique for the analysis of lipidomic profiles of human skin tissues.

Keywords: basal cell carcinoma; cutaneous squamous cell carcinoma; electroporation‐based biopsy; e‐biopsy; high‐throughput lipidomics; lipidomic profiles.

FIGURE 1

(A, B) E‐biopsy analysis and workflow. (A) Sample collection through pulsed electric field (PEF) application leads to the extraction of water‐soluble compounds that underwent subsequent UPLC‐MS‐MS and differential expression analysis. (B) Needle and electrode positioning on the skin during molecular harvesting by e‐biopsy.

FIGURE 2

(A–C) Overabundance plots comparing the distribution of lipid differential expression (both over‐ and under‐expression) p‐values between control (normal skin tissue), BCC, and cSCC tumor samples. A total of 13 samples and 168 lipids extracted by e‐biopsy were analyzed. The vertical red line marks the Student's T‐test p‐value cut‐off of 0.05. (A) cSCC versus Healthy, (B) BCC versus Healthy, and (C) cSCC versus BCC.

FIGURE 3

(A–C) Volcano plots and tables showing the fold change difference of lipid intensities. (A) cSCC vs. Healthy. (B) BCC versus Healthy. (C) cSCC versus BCC. Tables with lipid names correspond to lettered data points in the adjacent volcano plots. Fold change and p‐value data for lipids listed in the tables can be found in Table 2, Tables S2–S4.