ArticleAnalytical cellular pathology (Amsterdam)2026
BRAF Mutation Affects Intratumor Heterogeneity in Papillary Thyroid Carcinoma.
Article in Analytical cellular pathology (Amsterdam), 2026. 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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1 citing paper in PubMed.
- BRAF Mutation Affects Intratumor Heterogeneity in Papillary Thyroid Carcinoma.Analytical cellular pathology (Amsterdam) · 2026Article
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Abstract
backgroundIntratumor heterogeneity (ITH) plays an important role in patients' clinical outcomes. The prognostic impact of ITH and its influencing factors is unclear in papillary thyroid carcinoma (PTC), which deserves further investigation.
methodsThe Mutation Annotation Format (MAF) and clinical features were collected from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) cohort. We first assessed the influence of ITH on the prognosis of patients. We used the Mutant Allele Tumor Heterogeneity score to evaluate and represent ITH. Then we explored the potential factors associated with ITH. Finally, we predicted possible pathways involved in ITH.
resultsAmong 4 prognostic outcomes, higher ITH was mainly related to poor disease-free interval (DFI) (HR = 2.64, p = 0.01), and ITH had potential value for predicting DFI. Further, we identified BRAF mutation and thyroid differentiation score (TDS) as key factors independently influencing ITH (all p < 0.05), especially TDS, which had a favorable ability and obtained good net benefit in predicting ITH. TDS maintained a stable negative effect on ITH. In contrast, BRAF mutation positively correlated with ITH in univariable regression (β = 0.196). Through performing sensitivity, regression, subgroup, interaction effect, and mediation analyses, we identified that TDS played a suppression effect in the impact of BRAF mutation on ITH. Finally, we revealed that the propionate metabolism pathway was most strongly associated with ITH.
conclusionsITH is associated with DFI in patients with PTC and deserves more attention. TDS and BRAF mutation are the key influencing factors of ITH, but TDS exerts a suppression effect on the impact of BRAF mutation on ITH.
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