Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1533111
This article is part of the Research Topic Precision Medicine and Targeted Therapies in Gastrointestinal and Genitourinary Solid Tumors View all 4 articles

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

Provisionally accepted
Juan Ding Juan Ding Yunyan Teng Yunyan Teng Rongshu Cui Rongshu Cui Jin Liu Jin Liu Ke Xiao Ke Xiao Zhaogang Dong Zhaogang Dong Yi Zhang Yi Zhang *Xiaofei Xu Xiaofei Xu *
  • Qilu Hospital, Shandong University, Jinan, China

The final, formatted version of the article will be published soon.

    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. Serum EV RNA was extracted from four patients with GC and four healthy controls, followed by high-throughput RNA sequencing (RNA-seq). 37,684 lncRNAs were obtained, and 10 lncRNAs were selected based on the criteria (P < 0.05 and |log2FoldChange| ≥1) for further validation in training and validation sets using quantitative real-time RT-PCR (qRT-PCR). Results demonstrated that 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 (DFS) 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, natural kill T cells. In conclusion, 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.

    Keywords: gastric cancer, extracellular vesicles, long non-coding RNA, diagnosis, prognosis

    Received: 23 Nov 2024; Accepted: 06 Jan 2025.

    Copyright: © 2025 Ding, Teng, Cui, Liu, Xiao, Dong, Zhang and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yi Zhang, Qilu Hospital, Shandong University, Jinan, China
    Xiaofei Xu, Qilu Hospital, Shandong University, Jinan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.