Plasma extracellular vesicle mRNA profiling identified 483 differentially expressed genes linked to immunothrombosis that distinguished lung adenocarcinoma patients with VTE from those without.
Case-Control (n=21)
Does plasma extracellular vesicle mRNA profiling identify a pro-thrombotic molecular signature in lung adenocarcinoma patients with venous thromboembolism compared to thrombosis-free controls?
Plasma extracellular vesicle mRNA profiling identifies a distinct immunothrombotic signature that may improve VTE risk stratification in patients with lung adenocarcinoma.
Venous thromboembolism (VTE) significantly impacts lung adenocarcinoma outcomes, yet current predictive tools lack precision. We investigated plasma extracellular vesicle (EV) mRNA as a liquid biopsy source to identify a pro-thrombotic molecular profile in VTE patients. Within a prospective cohort of 260 patients, we performed a retrospective nested case–control study, matching 10 VTE cases with 11 thrombosis-free controls. Plasma EV-RNA was analyzed via high-throughput sequencing. Differentially expressed genes (DEGs) were integrated with functional enrichment and explored across public non-cancer VTE datasets, buffy coat samples, and cell lines. RNA-seq identified 483 DEGs within the VTE patient EV compartment, predominantly linked to neutrophil degranulation (NETosis), inflammation, and coagulation. We identified a set of EV-associated candidate genes (SELP, ELANE, MYL9, DNASE1L3) distinguishing cancer-associated thrombosis from non-malignant VTE, along with transcripts (TFPI, FCGR2A) selectively enriched within the EV compartment relative to circulating blood cells. P-selectin (SELP) was the only significantly increased marker, providing the strongest complementary support at the protein level. This molecular state was detectable prior to the occurrence of VTE. Plasma EVs capture a multicellular mRNA profile, reflecting the systemic immunothrombotic activation in lung adenocarcinoma. Despite sample size limitations, these findings should be considered exploratory and hypothesis-generating, but they suggest the EV-derived mRNA in combination with circulating markers such as SELP may provide a framework for future studies aimed at improving risk stratification.
Marcos‐Jubilar et al. (Fri,) conducted a case-control in Lung adenocarcinoma and venous thromboembolism (n=21). Plasma extracellular vesicle (EV) mRNA profile vs. Thrombosis-free controls was evaluated on Differentially expressed genes (DEGs) within the VTE patient EV compartment. Plasma extracellular vesicle mRNA profiling identified 483 differentially expressed genes linked to immunothrombosis that distinguished lung adenocarcinoma patients with VTE from those without.