LncRNAs in serum-derived extracellular vesicles are potential biomarker and correlated with immune infiltration in gastric cancer

Long non-coding RNAs (lncRNAs) in extracellular vesicles (EVs) have been confirmed as effective non-invasive biomarkers for multiple diseases. However, their expression and clinical value in gastric cancer (GC) remain poorly understood. Materials and

EV lncRNAs are prospective biomarker and correlated with immune cell infiltration in GC. It provides a foundation for the development of serum EV-targeted novel biomarkers and immunotherapy targets of GC.

Serum EV RNA was extracted from four patients with GC and four healthy controls, followed by high-throughput RNA sequencing. LncRNAs were further validated in training and validation sets using quantitative real-time reverse transcription polymerase chain reaction.

A total of 37,684 lncRNAs were obtained, and 10 lncRNAs were selected based on the criteria (P < 0.05 and |log2FoldChange| ≥1). Serum EV lncRNA RMRP, RPPH1, and linc-ROR were significantly higher in patients with GC than in those with chronic gastritis, atypical hyperplasia, or healthy control (all P < 0.05). Three lncRNAs were also significantly correlated with tumor diameter, lymphatic metastasis, distal metastasis, and TNM stage (all P < 0.05). The area under the curve (AUC) values for lncRNA RMRP, RPPH1, and linc-ROR were 0.727, 0.774, and 0.811, respectively. Corresponding sensitivity and specificity were 63.4% and 85.4%, 50.7% and 89.6%, and 78.5% and 66.7%. The combination of these three lncRNAs with carcinoembryonic antigen (CEA) yielded an AUC of 0.909, with a sensitivity and specificity of 83.3% each. Furthermore, high EV linc-ROR and RMRP expression levels were associated with worse disease-free survival and overall survival (OS). Univariate and multivariate Cox regression analyses confirmed that linc-ROR was the only independent prognostic factor for GC. Finally, the lncRNA-miRNA-mRNA network showed that three lncRNAs were predicted to interact with 15 miRNAs and 69 mRNAs. In addition, lncRNA RMRP and linc-ROR were correlated with immune cell infiltration, including neutrophils, central memory CD4 T cells, macrophage, and natural kill T cells.