Nondestructive protein sampling with electroporation facilitates profiling of spatial differential protein expression in breast tumors in vivo

Abstract

Excision tissue biopsy, while central to cancer treatment and precision medicine, presents risks to the patient and does not provide a sufficiently broad and faithful representation of the heterogeneity of solid tumors. Here we introduce e-biopsy—a novel concept for molecular profiling of solid tumors using molecular sampling with electroporation. As e-biopsy provides access to the molecular composition of a solid tumor by permeabilization of the cell membrane, it facilitates tumor diagnostics without tissue resection. Furthermore, thanks to its non tissue destructive characteristics, e-biopsy enables probing the solid tumor multiple times in several distinct locations in the same procedure, thereby enabling the spatial profiling of tumor molecular heterogeneity.We demonstrate e-biopsy in vivo, using the 4T1 breast cancer model in mice to assess its performance, as well as the inferred spatial differential protein expression. In particular, we show that proteomic profiles obtained via e-biopsy in vivo distinguish the tumors from healthy breast tissue and reflect spatial tumor differential protein expression. E-biopsy provides a completely new molecular sampling modality for solid tumors molecular cartography, providing information that potentially enables more rapid and sensitive detection at lesser risk, as well as more precise personalized medicine.

High-throughput metabolome comparison of cutaneous squamous cell carcinoma, basal cell carcinoma, and healthy skin with e-biopsy sampling

“…Here we present and perform the first comparative analysis of high-throughput metabolomic profiling of cSCC, BCC, and healthy skin tissues sampled with the e-biopsy method. This study contributes to the recently discovered capabilities of e-biopsy in transcriptomics, proteomics, and lipidomics [10][11][12][13]20 .…”

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

“…This also stands in contrast to previous lipid analysis studies that relied on serum samples, lacking a specific spatial context. This site‐specific sampling feature is advantageous as it enables the mapping of tumor heterogeneity and offers a deeper understanding of tumor complexities 26 …”

“…Here we perform a comparative analysis of the first high‐throughput lipidomic profiling of cSCC, BCC, and healthy skin tissue using e‐biopsy. These profiles were collected with the e‐biopsy approach, thus adding to previous e‐biopsy enabled profiling in transcriptomics, proteomics, and metabolomics 16,25–27 …”

“…The recent electroporation‐based biopsy sampling technique, e‐biopsy, that leverages cell permeabilization caused by electric fields for molecular harvesting, demonstrated its ability to sample molecular profiles that differentiate between cancerous and healthy skin. 25 , 26 , 27 Coupling this sampling method with UPLC‐MS‐MS, which has proven its ability to identify potential markers of skin cancer, 18 provides a promising direction for high‐throughput analysis of extractable molecules.…”

“…These profiles were collected with the e‐biopsy approach, thus adding to previous e‐biopsy enabled profiling in transcriptomics, proteomics, and metabolomics. 16 , 25 , 26 , 27 …”