Membrane Feature-Inspired Profiling of Extracellular Vesicles for Pancreatic Cancer Diagnosis

Abstract

Extracellular vesicles (EVs) have recently emerged as a promising tumor biomarker, and EV phenotyping offers many benefits for cancer diagnosis. However, the practicality of EV assays remains a challenge due to macromolecule disturbances, biomarker heterogeneities, and EV abundance limitations. Here, we demonstrate a membrane-based biosensor for precise and sensitive EV identification. The sensor synergistically integrates EV capture and detection by virtue of EV membrane features (membrane protein and lipid bilayer), comprising antibody-conjugated magnetic beads (AbMBs) and duplex-specific nuclease (DSN)-mediated amplification cycles. Bivalent cholesterol (biChol)-modified RNA–DNA duplexes are designed to insert into the EV membrane, transforming EV signals into RNA signals and initiating the signal amplification. The membrane-based signal production pattern eliminates protein interference. By employing four antibodies specific to PCa-related membrane proteins, the AbMB–biChol platform enables the successful differentiation and monitoring of PCa-related EVs and distinguishes PCa patients from healthy donors with improved efficacy, exhibiting superior efficiency over the analyses based on clinically used biomarker CA19-9 and PCa-related proteins. As such, the developed system has great potential for clinical PCa diagnosis.

Quantification of GPC1(+) Exosomes Based on MALDI-TOF MS In Situ Signal Amplification for Pancreatic Cancer Discrimination and Evaluation

“…It has been reported that in many developed countries, pancreatic cancer is among the top five causes of cancer death. 32 The fiveyear survival rate is less than 10%, and the survival time after diagnosis is 6 months. This is because patients with pancreatic cancer are usually diagnosed at an advanced stage, and in about 80−85% of patients, the tumor cannot be removed surgically.…”

Anti-Cancer Role and Therapeutic Potential of Extracellular Vesicles

“…Zinc transporter ZIP4 [ 37 ], cytoskeleton-associated protein 4, a novel Dickkopf1 receptor [ 96 ], and annexin A1 [ 200 ] are also potential biomarkers. A panel of miRNAs, mRNAs, and proteins derived from EVs is useful for the early diagnosis of pancreatic cancer [ 201 , 202 , 203 , 204 , 205 , 206 , 207 ]. It may be possible to predict treatment outcomes using EVs [ 208 ].…”

Microfluidic Platform for Profiling of Extracellular Vesicles from Single Breast Cancer Cells

“…All cells, both healthy and diseased, constantly secrete membrane-limited nanovesicles, referred to as extracellular vesicles (EVs), which vary in size (approximately ≤50 nm to 1 μm), lipid composition, and enclosed content such as nucleic acids, carbohydrates, lipids, and proteins, depending on the cell of origin and their biogenesis. , Originating from the plasma membrane or intracellular compartments, EVs carry information about the cell they derive from, in contrast to tissue-unrelated, dissolved proteins . EVs have received much attention as possible biomarkers as they circulate in most body fluids like urine, saliva, or blood , and are therefore easily accessible in non- or minimally invasive diagnostic samples using small liquid biopsies. Indeed, several studies confirmed their use in the diagnosis of pancreatic cancer, breast cancer, and glioblastoma .…”

“… 7 , 8 Originating from the plasma membrane or intracellular compartments, EVs carry information about the cell they derive from, in contrast to tissue-unrelated, dissolved proteins. 9 EVs have received much attention as possible biomarkers as they circulate in most body fluids like urine, 10 saliva, 11 or blood 12 , 13 and are therefore easily accessible in non- or minimally invasive diagnostic samples using small liquid biopsies. Indeed, several studies confirmed their use in the diagnosis of pancreatic cancer, 13 breast cancer, 14 and glioblastoma.…”

“… 9 EVs have received much attention as possible biomarkers as they circulate in most body fluids like urine, 10 saliva, 11 or blood 12 , 13 and are therefore easily accessible in non- or minimally invasive diagnostic samples using small liquid biopsies. Indeed, several studies confirmed their use in the diagnosis of pancreatic cancer, 13 breast cancer, 14 and glioblastoma. 15 EVs provide an enormous potential for sensitive diagnosis at an early point of time or for monitoring the progress of a therapy.…”