In-Depth Proteomic Analysis of Stage II Colorectal Cancer for the Identification of Recurrence Biomarkers in FFPE Tissue and Extracellular Vesicles

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma, Colon

DISEASE(S): Colorectal Cancer

SUBMITTER: Ana Montero Calle  

LAB HEAD: Rodrigo Barderas

PROVIDER: PXD060933 | Pride | 2026-05-03

REPOSITORIES: Pride