Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• There is a significant unmet clinical need for advanced cancer detection tools.
• Extracellular vesicles and particles (EVPs) are increasingly recognized for their diagnostic potential.

Purpose of the Study:

• To investigate the proteomic profiles of EVPs from various human samples for cancer detection.
• To identify reliable pan-EVP markers and tumor-specific EVP proteins.

Main Methods:

• Proteomic analysis of 426 human tissue explant (TE) and plasma samples.
• Identification of traditional and novel pan-EVP markers (e.g., CD9, ACTB).
• Machine-learning classification of EVP cargo for cancer detection and origin determination.

Main Results:

• Identified novel pan-EVP markers: ACTB, MSN, and RAP1B.
• TE-derived EVPs distinguished tumors from normal tissues with 90% sensitivity and 94% specificity.
• Plasma-derived EVPs achieved 95% sensitivity and 90% specificity in cancer detection.
• Defined tumor-type-specific EVP panels for classifying tumors of unknown origin.

Conclusions:

• EVP proteins are reliable biomarkers for sensitive and specific cancer detection.
• EVP proteomic profiling can aid in determining cancer type and origin.
• EVPs represent a promising avenue for developing improved liquid and tissue biopsy tools.