Diagnostic efficacy of an extracellular vesicle-derived lncRNA-based liquid biopsy signature for the early detection of early-onset gastric cancer
Menée à partir de données transcriptomiques portant sur 37 échantillons gastriques sains et 74 échantillons de tumeurs gastriques de survenue précoce ou tardive puis à partir d'échantillons sanguins prélevés sur 1 490 patients supplémentaires, cette étude évalue l'efficacité d'une biopsie liquide, basée sur de longs ARN non codants issus de vésicules extracellulaires, pour détecter très tôt un cancer gastrique de survenue précoce
Background : Early-onset gastric cancer (EOGC) is a lethal malignancy. It differs from late-onset gastric cancer (LOGC) in clinical and molecular characteristics. The current strategies for EOGC detection have certain limitations in diagnostic performance due to the rising trend in EOGC.
Objective : We developed a liquid biopsy signature for EOGC detection.
Design : We use a systematic discovery approach by analysing genome-wide transcriptomic profiling data from EOGC (n=43), LOGC (n=31) and age-matched non-disease controls (n=37) tissue samples. An extracellular vesicle-derived long non-coding RNA (EV-lncRNA) signature was identified in blood samples from a training cohort (n=299), and subsequently confirmed by qPCR in two external validation cohorts (n=462 and n=438), a preoperative/postoperative cohort (n=66) and a gastrointestinal tumour cohort (n=225).
Results : A three EV-lncRNA (NALT1, PTENP1 and HOTTIP) liquid biopsy signature was developed for EOGC detection with an area under the receiver operating characteristic curve (AUROC) of 0.924 (95% CI 0.889 to 0.953). This EV-lncRNA signature provided robust diagnostic performance in two external validation cohorts (Xi’an cohort: AUROC, 0.911; Beijing cohort: AUROC, 0.9323). Furthermore, the EV-lncRNA signature reliably identified resectable stage EOGC patients (stage I/II) and demonstrated better diagnostic performance than traditional GC-related biomarkers in distinguishing early-stage EOGC (stage I) from precancerous lesions. The low levels of this biomarker in postsurgery and other gastrointestinal tumour plasma samples indicated its GC specificity.
Conclusions : The newly developed EV-lncRNA signature effectively identified EOGC patients at a resectable stage with enhanced precision, thereby improving the prognosis of patients who would have otherwise missed the curative treatment window.
Gut , résumé, 2025