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Proteomic profiling of exosomes from specimen-derived blood in colorectal cancer

ABSTRACT: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, necessitating the discovery of novel prognostic biomarkers. Tumor-derived exosomes are emerging as rich reservoirs of protein biomarkers; however, accessing sufficient quantities of tumor-proximal material remains challenging. In this study, we introduce specimen-derived blood (sdBlood), collected immediately after surgical resection of CRC specimens, as a novel and enriched source for tumor-proximal exosome isolation. We employed label-free LC-MS/MS-based proteomics to comprehensively profile the exosomal proteome from sdBlood and compared it with matched peripheral venous blood to identify differentially enriched proteins. Our analyses revealed a distinct proteomic signature in sdBlood-derived exosomes, with several proteins showing significant prognostic potential in publicly available CRC cohorts. This project encompasses the full proteomic dataset generated from these analyses. The data provide a valuable resource for understanding the tumor microenvironment and support the potential of sdBlood as a promising liquid biopsy substrate for prognostic biomarker discovery in colorectal cancer.

ORGANISM(S): Homo Sapiens

SUBMITTER: Muqing Yang

PROVIDER: PXD080312 | iProX | Mon Jun 29 00:00:00 GMT+01:00 2026

REPOSITORIES: iProX

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Project description:Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, with stage II CRC patients presenting unique challenges due to their heterogeneous outcomes. Despite curative surgical resection, 15-20% of stage II CRC patients experience recurrence within five years of diagnosis. Current prognostic models, based on clinicopathologic features such as vascular invasion, poor differentiation, and adverse molecular profiles, lack precision in predicting recurrence, highlighting the need for other complementary tools. Advances in proteomics have positioned formalin-fixed paraffin-embedded (FFPE) tissues and small extracellular vesicles (sEVs) as promising sources for biomarker identification. FFPE tissues offer a wealth of retrospective diagnostic material, while sEVs, particularly exosomes, encapsulate tumor-derived proteins and nucleic acids, providing minimally invasive insights into the tumor microenvironment. Proteomic profiling of these samples should allow the identification of molecular alterations linked to tumor aggressiveness and recurrence, paving the way for novel diagnostic and prognostic applications. In this study, we here combine proteomics analyses of paired FFPE tissues and sEVs to identify stage II CRC associated biomarkers and tumor biopsies, plasma of CRC patients and controls, and immunohistochemistry and in vitro and in vivo analyses to validate proteomics results. Among the identified candidates, CDCA2 emerged as a interesting driver of tumor formation, progression, and metastasis in CRC. Transient knockdown experiments demonstrated that its depletion impaired key tumorigenic processes, including proliferation, adhesion, migration, and invasion. Additionally, this study validated MANF as a plasma biomarker capable of distinguishing recurrent from non-recurrent CRC patients, offering potential for improving patient stratification and personalized treatment strategies in combination with other markers. Interestingly, our multifaceted approach allowed the identification of dysregulated proteins associated to CRC recurrence.

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Proteomic profiling of exosomes from specimen-derived blood in colorectal cancer

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