Diagnostic efficacy of an extracellular vesicle-derived lncRNA-based liquid biopsy signature for the early detection of early-onset gastric cancer

Xin Guo ^1,2,3, Weidong Wang ², Xin Cheng ⁴

⁰Department of General Surgery, Xijing 986th Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.

Gut +

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March 20, 2025

View abstract on PubMed

Summary

A novel liquid biopsy signature using three extracellular vesicle-long non-coding RNAs (EV-lncRNAs) effectively detects early-onset gastric cancer (EOGC). This blood-based test aids in identifying resectable EOGC, improving patient prognosis and timely treatment.

Area Of Science

Oncology
Molecular Diagnostics
Genomics

Background

Early-onset gastric cancer (EOGC) presents unique clinical and molecular features compared to late-onset gastric cancer (LOGC).
Current diagnostic methods for EOGC face limitations, particularly given the increasing incidence of this malignancy.
There is a critical need for improved diagnostic strategies for EOGC to facilitate early detection and intervention.

Purpose Of The Study

To develop and validate a novel liquid biopsy signature for the accurate detection of early-onset gastric cancer (EOGC).
To identify specific extracellular vesicle-derived long non-coding RNAs (EV-lncRNAs) that can serve as biomarkers for EOGC.
To assess the diagnostic performance of the developed signature in distinguishing EOGC from other conditions and identifying resectable stages.

Main Methods

Genome-wide transcriptomic profiling of tissue samples from EOGC, LOGC, and control groups was analyzed.
An extracellular vesicle-derived long non-coding RNA (EV-lncRNA) signature was identified using blood samples from a training cohort.
The signature's diagnostic accuracy was validated in two independent external cohorts using quantitative polymerase chain reaction (qPCR).

Main Results

A three-EV-lncRNA signature (NALT1, PTENP1, HOTTIP) demonstrated high diagnostic performance for EOGC detection, with an AUROC of 0.924.
The signature showed robust diagnostic accuracy in external validation cohorts (Xi'an: AUROC 0.911; Beijing: AUROC 0.9323).
The EV-lncRNA signature effectively identified resectable EOGC (Stage I/II) and outperformed traditional biomarkers in differentiating early-stage EOGC from precancerous lesions, showing specificity in plasma samples.

Conclusions

The developed EV-lncRNA liquid biopsy signature provides a precise and effective method for detecting early-onset gastric cancer (EOGC).
This non-invasive diagnostic tool can identify patients with resectable EOGC, enabling timely curative treatment.
The enhanced precision offered by this signature has the potential to significantly improve patient prognosis by preventing missed opportunities for curative intervention.

Keywords:

CANCER CEA GASTRIC CANCER GASTROINTESTINAL CANCER

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