ArticleScientific reports2026
Methylation heterogeneity of the AQP1 promoter as a candidate prognostic biomarker in cholangiocarcinoma.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Cholangiocarcinoma (CC) is an aggressive cancer with limited prognostic biomarkers. Aquaporin 1 (AQP1), a water channel protein, is implicated in cancer progression. Moreover, DNA methylation plays a key role in epigenetic gene regulation. Therefore, the present study aimed to investigate the prognostic significance of AQP1 promoter methylation haplotypes in CC using high-resolution bisulfite amplicon sequencing. AQP1 mRNA expression in 102 patients was evaluated first to examine its prognostic impact. Subsequently, methylation haplotypes in non-neoplastic and neoplastic tissues from 96 patients were analyzed. Methylation heterogeneity was assessed using t-distributed stochastic neighbor embedding (t-SNE) and k-means clustering. Although AQP1 mRNA expression alone was not a robust independent prognostic factor, a t-SNE-based classification of the methylation signature identified two subgroups with distinct overall survival in both non-neoplastic and neoplastic tissues. Multivariate analysis using Firth's penalized Cox regression indicated that this methylation signature was independently associated with prognosis (hazard ratio 0.322, p = 0.001). Similar haplotype alterations were observed in non-neoplastic and neoplastic tissues, consistent with the possibility of an epigenetic field effect. These findings suggest that evaluating the methylation signature of the AQP1 promoter may support future less-invasive prognostic assessment and risk stratification, suggesting its potential utility as a candidate biomarker in CC.
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