ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2025
COPS5 inhibition synergizes with the antitumor effect of trastuzumab by PTEN upregulation in HER2-amplified gastric cancer.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2025. 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
17 authors.
Funding
Abstract
backgroundCOP9 Signalosome Subunit 5 (COPS5) is a deubiquitinating enzyme that induces chemotherapy resistance. The role of COPS5 amplification in patients with gastric cancer (GC) and its therapeutic potential in HER2-amplified GC models have not been explored.
methodsThe Cancer Genome Atlas (TCGA) data were analyzed to assess the clinical relevance of COPS5 amplification in patients with GC. Functional studies using HER2-amplified GC cell lines and xenograft models evaluated the effects of COPS5 inhibition (CSN5i-3), alone or in combination with trastuzumab.
resultsIn the curated stomach adenocarcinoma cohort (n = 294) from TCGA datasets, COPS5 amplification was significantly more frequent in patients with HER2 amplification (10.5% vs. 2.7%, P = 0.040) and was associated with worse disease-free survival after surgery (median 12.6 vs. 45.2 months, P = 0.012) and overall survival (median 21.4 months vs. not reached, P = 0.004). In HER2-amplified GC cell lines, CSN5i-3 treatment synergized with the antiproliferative effect of trastuzumab. Mechanistically, COPS5 knockout enhanced PTEN expression by ubiquitin-mediated SNAIL degradation, suppressing the AKT downstream pathway. The combination effect was dependent on PTEN expression. Accordingly, COPS5 knockout enhanced the efficacy of AKT inhibitors. In a xenograft model, the combination of CSN5i-3 and trastuzumab demonstrated synergistic antitumor effects compared to monotherapy.
conclusionsCOPS5 amplification was significantly more prevalent in patients with HER2 amplification and was associated with poor outcomes after surgery. The synergistic antiproliferative effect of COPS5 inhibition and trastuzumab was attributed to increased PTEN expression via SNAIL ubiquitination, resulting in the inhibition of the AKT pathway, warranting further clinical studies in patients with HER2-positive GC.
Indexed as
Identifiers
41039054What 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.