ArticleCell communication and signaling : CCS2026
Harnessing tumor-associated exosomal aminopeptidase N as a dual-function tool for monitoring and tackling chemoresistance in gastric cancer.
Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
Chemoresistance remains a major obstacle to effective treatment in gastric cancer (GC), with a notable scarcity of clinically applicable biomarkers and therapeutic targets. In this study, we employed an integrated proteomic approach analyzing paired serum samples from GC patients at disease control and progressive disease stages during chemotherapy, exosomes from chemoresistant and chemosensitive GC cells, and corresponding whole-cell proteomes to identify tumor-associated exosomal drivers of chemoresistance. Cross-dataset integration identified aminopeptidase N (APN/CD13) as selectively enriched under chemoresistant conditions. Functional validation demonstrated that APN depletion via shRNA or CRISPR restored cisplatin sensitivity in refractory cells, whereas APN overexpression conferred chemoprotection. A neutralizing anti-APN monoclonal antibody resensitized resistant cells and showed superior efficacy compared with the broad-spectrum peptidase inhibitor bestatin in vivo. Mechanistically, APN sustained a ferroptosis-suppressive state: its inhibition increased ROS and lipid peroxidation, shifted transcriptomic profiles toward pro-ferroptotic pathways, and downregulated the lipid peroxide detoxifier AKR1C2, which correlated with poor prognosis and APN expression in the TCGA-STAD cohort. Exosomal transfer assays confirmed that APN-enriched vesicles disseminated chemoresistance and ferroptosis evasion to sensitive cells, accelerating tumor progression during chemotherapy, whereas APN-deficient exosomes lacked this capacity. Clinically, serum exosomal APN levels robustly distinguished progressive disease from disease control in a cohort of 105 patients (AUC = 0.85; optimal cutoff 0.936 ng/mL). Collectively, these findings position exosomal APN as a dual-function tool, serving both as a dynamic liquid biopsy biomarker and an antibody-targetable node for monitoring and overcoming chemoresistance in gastric cancer.
Indexed as
Identifiers
42458480What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.