Molecular profiling and prognostic significance of gastric cancer subtypes based on extracellular vesicle-related characteristics
5 affiliations
- 1Zhejiang Cancer Hospital; Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences , ,
- 2Beijing Friendship Hospital, Capital Medical University , ,
- 3Department of Gastrointestinal Surgery, The First Affiliated Hospital of Ningbo University , , ,
- 4Division of General, Oncological, Mini-Invasive and Obesity Surgery, University of Campania “Luigi Vanvitelli” , ,
- 5Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University , ,
Abstract
Background: Gastric cancer (GC) is a molecularly heterogeneous disease. This study aims to explore whether endocytosis pathway-associated genes and immune checkpoint-related features were linked to GC subtypes and prognosis.
Methods: Public transcriptomic datasets from TCGA and GEO were analyzed. ssGSEA was applied to predefined endocytosis-related gene sets, and NMF was used to identify molecular subtypes. Survival, tumor microenvironment features, tumor mutation burden, microsatellite instability, and differentially expressed genes were evaluated. A three-gene prognostic model was developed and assessed through retrospective internal and external validation across public cohorts for prognostic association only.
Results: Two endocytosis-related subtypes were identified. The Group 1 subtype showed higher pathway activity, more immunosuppressive microenvironmental features, higher expression of selected immune checkpoint-related markers, and poorer survival. The Group 2 subtype showed lower pathway activity and more favorable outcomes. A three-gene signature (NRP1, SERPINE1, and MISP3) stratified patients into higher-risk and lower-risk groups across retrospective cohorts. Higher-risk cases were associated with worse overall survival and enrichment of epithelial-mesenchymal transition- and immune evasion-related pathways. This retrospective cross-cohort validation suggests that the prognostic signal was not restricted to a single dataset, but it does not demonstrate prospective clinical validity, analytical validity, or readiness for clinical implementation.
Conclusions: Endocytosis-related molecular patterns may be associated with distinct biological and prognostic features in GC. The identified subtypes and prognostic signature should be interpreted as exploratory, hypothesis-generating findings that warrant further prospective, functional, and assay-level validation.
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BibTeX
@article{ding2026molecular,
title = {{Molecular profiling and prognostic significance of gastric cancer subtypes based on extracellular vesicle-related characteristics}},
author = {Guangyu Ding and Chenjie Xu and Xingmao Huang and Federico Maria Mongardini and Pengfei Yu and Chengkang Zhu and Hongtao Wang and Zequan Wu and Shengxin Fang and Xinyi Lei and Minji Xu and Salvatore Tolone and Ludovico Docimo and Li Min and Ling Huang},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1948199},
url = {https://europepmc.org/article/PMC/PMC13669850},
note = {CC BY},
}
RIS
TY - JOUR
TI - Molecular profiling and prognostic significance of gastric cancer subtypes based on extracellular vesicle-related characteristics
AU - Guangyu Ding
AU - Chenjie Xu
AU - Xingmao Huang
AU - Federico Maria Mongardini
AU - Pengfei Yu
AU - Chengkang Zhu
AU - Hongtao Wang
AU - Zequan Wu
AU - Shengxin Fang
AU - Xinyi Lei
AU - Minji Xu
AU - Salvatore Tolone
AU - Ludovico Docimo
AU - Li Min
AU - Ling Huang
PY - 2026
DA - 2026/10/01
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1948199
UR - https://europepmc.org/article/PMC/PMC13669850
AB - Background: Gastric cancer (GC) is a molecularly heterogeneous disease. This study aims to explore whether endocytosis pathway-associated genes and immune checkpoint-related features were linked to GC subtypes and prognosis. Methods: Public transcriptomic datasets from TCGA and GEO were analyzed. ssGSEA was applied to predefined endocytosis-related gene sets, and NMF was used to identify molecular subtypes. Survival, tumor microenvironment features, tumor mutation burden, microsatellite instability, and differentially expressed genes were evaluated. A three-gene prognostic model was developed and assessed through retrospective internal and external validation across public cohorts for prognostic association only. Results: Two endocytosis-related subtypes were identified. The Group 1 subtype showed higher pathway activity, more immunosuppressive microenvironmental features, higher expression of selected immune checkpoint-related markers, and poorer survival. The Group 2 subtype showed lower pathway activity and more favorable outcomes. A three-gene signature (NRP1, SERPINE1, and MISP3) stratified patients into higher-risk and lower-risk groups across retrospective cohorts. Higher-risk cases were associated with worse overall survival and enrichment of epithelial-mesenchymal transition- and immune evasion-related pathways. This retrospective cross-cohort validation suggests that the prognostic signal was not restricted to a single dataset, but it does not demonstrate prospective clinical validity, analytical validity, or readiness for clinical implementation. Conclusions: Endocytosis-related molecular patterns may be associated with distinct biological and prognostic features in GC. The identified subtypes and prognostic signature should be interpreted as exploratory, hypothesis-generating findings that warrant further prospective, functional, and assay-level validation.
SN - 2234-943X
ER -