Key result
Extracellular vesicles in HFrEF with incident cancer show distinct proteomic profiles and blunt cancer cell apoptosis.
Why the study?
Previous studies found increased cancer incidence in patients with HFrEF, prompting exploration of the biological correlates of this association in humans.
Do circulating extracellular vesicle-enriched fractions from HFrEF patients with incident cancer exhibit a distinct proteomic signature and modulate human cancer cell biology compared to matched HFrEF controls without cancer?
Case-Control
Do circulating extracellular vesicle-enriched fractions from HFrEF patients with incident cancer exhibit a distinct proteomic signature and modulate human cancer cell biology compared to matched HFrEF controls without cancer?
Circulating extracellular vesicle-enriched fractions from patients with HFrEF and incident cancer display a distinct proteomic signature (148 differentially expressed proteins) and modulate apoptosis and gene expression in human cancer cell lines.
No specific plasma signature identified cancer risk in HFrEF; leaves open shared biology and warrants prospective validation.
Aims Previous studies found increased cancer incidence in patients with heart failure with reduced ejection fraction (HFrEF). We sought to explore the biological correlates of the association of HFrEF with cancer in humans. Methods and results: Among participants in the GISSI-HF trial with HFrEF and available baseline plasma samples, we selected those who developed solid cancer (cases) and matched them with controls without cancer by age, sex, NYHA class, and follow-up duration. We isolated the plasma extracellular vesicle (EV)-enriched fraction, in which EVs were confirmed by western blot for CD9, FLOTILLIN-1, ALIX and TSG101, and by nanoparticle tracking analysis (mean particle diameter <200 nm). The protein content of EV preparations was characterized by nanoliquid chromatography-high resolution tandem mass spectrometry. Of 940 identified proteins, 148 were differentially expressed between EV preparations from cases (EVs-cases) and controls (EVs-controls) and were related to biological functions implicated in cancer growth, particularly apoptosis and spliceosome/transcriptome regulation. Next, we explored the effects of EVs-cases and EVs-controls in MCF7 breast cancer cells and run confirmatory experiments with another 2 cell lines, HCT116 (colon) and A549 (lung). Apoptosis, as determined by caspase 3 cleavage, was blunted by EVs-cases in MCF7, but not in HCT116 and A549 cells. Screening qPCR pointed out NR3C1, encoding glucocorticoid receptor, as a spliceosome/transcription modulator affected by EVs-cases. Targeted qPCR confirmed that it was reduced by EVs-cases in A549 cells. Conclusions Circulating EV-enriched fractions from patients with HFrEF and incident cancer have a distinct proteomic signature and might modulate human cancer cell biology.
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Bianconi et al. (2026) conducted a case-control in Heart failure with reduced ejection fraction (HFrEF) and incident solid cancer. Incident solid cancer (plasma extracellular vesicle-enriched fraction from cases) vs. No incident cancer (matched HFrEF controls without cancer) was evaluated on Differential protein expression in plasma extracellular vesicle-enriched fractions and functional effects on cancer cell lines. Plasma EV-enriched fractions from HFrEF patients with incident cancer had 148 of 940 proteins differentially expressed vs controls and blunted apoptosis in MCF7 breast cancer cells.
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