ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2025
A mutational signature and ARID1A mutation associated with outcome in hepatocellular carcinoma.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Abstract
objectiveThe prognosis of hepatocellular carcinoma (HCC) is poor and there is no stable and reliable molecular biomarker for evaluation. This study attempted to find reliable prognostic markers from tumor mutational profiles.
methodsA total of 362 HCC samples with whole-exome sequencing were collected as discovery datasets, and 200 samples with targeted sequencing were used for validation of the relevant results. All HCC samples were obtained from previously published studies. Bayesian non-negative matrix factorization was used to extract mutational signatures, and multivariate Cox regression models were utilized to identify the prognostic role of mutational factors. Gene set enrichment analysis was employed to discover potential signaling pathways associated with specific mutational groups.
resultsIn the HCC discovery dataset, a total of four mutational signatures (i.e., signatures 4, 6, 16, and 22) were extracted, of which signature 16 characterized by T>C mutations was observed to be associated with favorable HCC prognosis, and this correlation was also found in the validation dataset. Further analysis showed that patients with ARID1A mutations exhibited inferior survival outcomes in both discovery and validation datasets. Mechanistic exploration revealed that the presence of signature 16 was associated with better immune infiltration and tumor immunogenicity, while patients with ARID1A mutations were away from these favorable immunological features.
conclusionBy integrating somatic mutation data and clinical information of HCC, this study identified that signature 16 and ARID1A mutations were associated with better and worse outcomes respectively, providing a basis for prognosis prediction and clinical treatment strategies of HCC.
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