ORIGINAL RESEARCH article
Front. Oncol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1597187
This article is part of the Research TopicDemystifying Fundamental Mechanisms of anticancer drug resistance in Gastrointestinal OncologyView all 5 articles
Cell-In-Cell-Associated lncRNA Signature Predicts Prognosis and the Immune Response in Gastric Cancer
Provisionally accepted
- 1Southwest Medical University, Luzhou, Sichuan, China
- 2The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
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Background: Gastric cancer (GC) remains a leading cause of cancer-related mortality, with heterogeneous molecular features and limited therapeutic efficacy of immune checkpoint inhibitors (ICIs). Cell-in-cell (CIC) structures and long non-coding RNAs (lncRNAs) are emerging players in tumor progression and immune modulation, yet their combined role in GC remains unexplored. Methods: Using TCGA-GC data, we identified CIC-related lncRNAs (CICRlncRNAs) via Pearson correlation and Cox regression. A prognostic model was constructed and validated for risk stratification, immune microenvironment analysis (CIBERSORT, ESTIMATE, TIDE), and drug sensitivity prediction (oncoPredict). Functional assays (qRT-PCR, CCK-8, Transwell) validated key CICRlncRNAs in vitro.Results: A 3-CICRlncRNA signature (AP003392.1, AP000695.2, AL161785.1) stratified GC patients into high- and low-risk groups with distinct survival outcomes (p < 0.001). High-risk patients exhibited immunosuppressive TME features and poorer ICI response (TIDE, P < 0.001). AP000695.2 knockdown suppressed GC cell proliferation, migration, and invasion (P < 0.01). Differential drug sensitivities (e.g., gefitinib for low-risk; dasatinib for high-risk) were identified.Conclusion: CICRlncRNAs are novel prognostic biomarkers and immunotherapeutic predictors in GC, linking CIC phenomena to immune evasion. The risk model guides precision therapy by integrating molecular subtypes, TME features, and drug responses.
Keywords: gastric cancer, Cell-in-cell, long non-coding RNAs, Tumor Microenvironment, personalized therapy
Received: 20 Mar 2025; Accepted: 11 Apr 2025.
Copyright: © 2025 Lin, Wu and Zhao. 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: Zhengfei Zhao, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China
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