ArticleCancer science2026
CpG Methylation-Driven Pleiotropic Spliced Isoforms of PRSS3 Facilitate Gastric Intratumor Heterogeneity and Metastasis.
Article in Cancer science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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
2 citing papers in PubMed.
- PRSS1 isoforms promote type 2 immune responses in IgG4-related disease.Genes and immunity · 2026Article
- Integrated microbial and transcriptomic profiling reveals distinct correlations in atrophic gastritis associated with liver cirrhosis.Frontiers in cellular and infection microbiology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
Investigating the phenotypic contribution of gene-spliced isoforms to tumor cellular heterogeneity can facilitate the development of innovative strategies for precision medicine. Serine protease 3 (PRSS3), a trypsin-like protease with four spliced variants (PRSS3-SVs: PRSS3-V1 to V4), plays diverse biological roles in cancer progression. Herein, we systematically analyzed the expression patterns and functional implications of PRSS3-SVs in gastric cancer (GC) using an integrative approach that combined bioinformatic analyses, CpG site-specific methylation detection, splice-specific qPCR, isoform-based methodologies, and multiple functional assays. Our findings revealed that differentially expressed PRSS3 isoforms, predominantly PRSS3-V1 and PRSS3-V2, are regulated by intragenic methylation and exert pleiotropic roles in GC. Overexpression of PRSS3 transcripts suppressed GC cell proliferation via the NF-κB signaling pathway, while exerting distinct effects on matrix metalloproteinase-associated cell migration and invasion. Clinically, patients with low PRSS3-V1 or high PRSS3-V2 expression exhibited poorer survival outcomes, and the expression difference between these two transcripts was identified as an independent prognostic indicator for GC patients. Epigenetically, differential methylation patterns within PRSS3 enabled stratification of GC patients into subgroups characterized by either high-methylation with low-expressed PRSS3-SVs or low-methylation with high-expressed PRSS3-SVs. The UHRF1/DNMT1 complex was found to mediate CpG site methylation and regulate PRSS3 transcripts, particularly silencing PRSS3-V1 through intragenic CpG methylation. This methylation pattern was associated with reduced survival rates and further validated its correlation with tumor metastasis in an independent cohort (n = 243). Our study elucidates that methylation-regulated alternative splicing contributes to phenotypic heterogeneity in GC, highlighting its potential advantage over differentially expressed genes in improving stratification strategies for precision oncology.
Indexed as
Identifiers
What 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.