Molecular Harvesting of Proteins with Electroporation In Vivo Facilitates the Profiling of Spatial Differential Protein Expression in Tumors

Abstract

Background. 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 sampled solid tumors. Methods. Here we introduce e-biopsy – a novel concept for molecular profiling of solid tumors using molecular extraction with electroporation. As e-biopsy provides access to the molecular composition of a solid tumor, it potentially facilitates tumor diagnostics without tissue resection. Furthermore, thanks to its less invasive 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.Results. 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 tissue and reflect spatial tumor differential protein expression.Conclusions. E-biopsy provides a completely new molecular cartography modality for solid tumors, providing information that potentially enables more sensitive detection, at lesser risk, as well as more precise personalized medicine.

Deciphering dermatological distinctions: Cornulin as a discriminant biomarker between basal cell carcinoma and squamous cell carcinoma detected through e‐biopsy and machine learning

“…Recently, we introduced a novel, minimally invasive tissue sampling approach with molecular biopsy using electroporation, termed 'e-biopsy', that selectively extracts liquids with informative proteomes in animal models in liver cancer 14 and brain melanoma 15 in vitro and in breast cancer in vivo, enabling in vivo spatial mapping of differential protein expression. 16 Electroporation-based technologies have been successfully used to permeabilize the cell membrane in vivo, enabling a broad set of applications ranging from tumour ablation to targeted delivery of molecules to cell populations and tissues. 17 However, to the best of our knowledge, such a technology is not yet available and has not been reported in the literature for minimally invasive human tissue molecular sampling.…”

Proteome sampling with e-biopsy enables differentiation between cutaneous squamous cell carcinoma and basal cell carcinoma

“…We have previously developed protocols for targeted delivery of electric fields to tissues to induce focused electroporation at predetermined regions in organs 23 . More recently, we have shown that electroporation-based molecular sampling, termed "e-biopsy", selectively extracts liquids from solid tissues with informative proteomes in animal models in liver cancer 24 and brain melanoma 25 in vitro and from breast cancer in vivo, enabling in vivo spatial mapping of differential protein expression 26 . To the best of our knowledge, such a technology…”