Louie Leetal, Wise Julia, Berl Ariel, Shir-Az Ofir, Kravtsov Vladimir, Yakhini Zohar, Shalom Avshalom, Golberg Alexander, Vitkin Edward
School of Mechanical Engineering, Tel Aviv University, Tel Aviv, Israel.
Department of Plastic Surgery, Meir Medical Center, Kfar Sava, Israel.
Cell Mol Bioeng. 2025 Apr 3;18(2):185-195. doi: 10.1007/s12195-025-00846-1. eCollection 2025 Apr.
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.
皮肤鳞状细胞癌（cSCC）和基底细胞癌（BCC）发病率不断上升，使得标准组织病理学诊断方法成为瓶颈。利用组织分子信息进行诊断提供了一种有前景的替代方法。更快的样本采集和高通量分子鉴定可以改善对日益增多的肿瘤的处理。本研究旨在：（i）确认电子活检技术采集代谢物的能力；（ii）获得cSCC、BCC和健康皮肤组织的高分辨率代谢组学图谱；（iii）对所采集的图谱进行比较分析。
使用基于电穿孔的活检（电子活检）这一微创采样工具，从12名患者的13个组织样本（cSCC、BCC和健康皮肤）中采集肿瘤标本。采用超高效液相色谱和串联质谱（UPLC-MS-MS）对所得代谢组学图谱进行分子鉴定和定量分析。
我们在此报告了在12名患者的13个组织样本中鉴定出的2325种小分子代谢物（301种具有高可信度）的测量结果。比较分析确定了34种显著（p < 0.05）差异表达的高可信度代谢物。总体而言，我们观察到与健康组织相比，cSCC和BCC中表达较高的代谢物数量更多，这些代谢物属于氨基酸、肽及其类似物亚类。
这些发现证实了电子活检技术获得适合下游生物信息学分析的高分辨率代谢组学图谱的能力。这突出了电子活检结合UPLC-MS-MS在皮肤癌中进行快速、高通量代谢组学分析的潜力，并支持其作为标准组织病理学有前景的诊断替代方法的实用性。
在线版本包含可在10.1007/s12195-025-00846-1获取的补充材料。
