ArticleThe Journal of clinical endocrinology and metabolism2022
Prognostic Role of Targeted Methylation Analysis in Paraffin-embedded Samples of Adrenocortical Carcinoma.
Article in The Journal of clinical endocrinology and metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study.The lancet. Diabetes & endocrinology · 2023Trial
- A multi-centre, prospective trial of a methylation-based liquid biopsy for early detection of liver cancer in high-risk populations.Clinical and translational medicine · 2026Article
- S-GRAS score and the complementary prognostic value of neutrophil-to-lymphocyte ratio in adrenocortical carcinoma: evidence for a synergistic interaction.Frontiers in endocrinology · 2026Observational
- Recent advances on the role of G0S2.Discover oncology · 2025Review
- Updates on WHO 5th edition classification, molecular characteristics and tumor microenvironment of adrenocortical carcinomas.Endocrine journal · 2025Review
- Contrast CT radiomic features add value to prediction of prognosis in adrenal cortical carcinoma.Endocrine · 2024Article
- Paired Box 5 (PAX5) Gene Has Diagnostic and Prognostic Potential in Nasopharyngeal Carcinoma.International journal of general medicine · 2024Article
- Advances in translational research of the rare cancer type adrenocortical carcinoma.Nature reviews. Cancer · 2023Review
- G0S2 promotes antiestrogenic and pro-migratory responses in ER+ and ER- breast cancer cells.Translational oncology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
contextAdrenocortical carcinoma (ACC) is a rare aggressive disease with heterogeneous prognoses. Previous studies identified hypermethylation in the promoter region of specific genes to be associated with poor clinical outcome.
objectiveComparative analysis of promising hypermethylated genes as prognostic markers and evaluation of their added value to established clinical prognostic tools.
designWe included 237 patients with ACCs. Tumor DNA was isolated from formalin-fixed paraffin-embedded (FFPE) samples. Targeted pyrosequencing was used to detect promoter region methylation in 5 preselected genes (PAX5, GSTP1, PYCARD, PAX6, G0S2). The prognostic role of hypermethylation pattern was compared with the Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score. Primary endpoints were progression-free (PFS) and overall survival (OS), with disease-free (DFS) as secondary endpoint.
resultsA total of 27.9%, 13.9%, 49%, 49%, and 25.3% of cases showed hypermethylation in PAX5, GSTP1, PYCARD, PAX6, and G0S2, respectively. Hypermethylation in all individual genes-except GSTP1-was significantly associated with both PFS and OS-with hazard ratios (HR) between 1.4 and 2.3. However, only hypermethylation of PAX5 remained significantly associated with OS (P = 0.013; HR = 1.95, 95% CI, 1.2-3.3) in multivariable analysis. A model for risk stratification was developed, combining PAX5 methylation status and S-GRAS groups, showing improved prognostic performance compared to S-GRAS alone (Harrell's C index: OS = 0.751, PFS = 0.711, DFS = 0.688).
conclusionsThis study demonstrated that hypermethylation in PAX5 is associated with worst clinical outcome in ACC, even after accounting for S-GRAS score. Assessing methylation in FFPE material is straightforward in the clinical setting and could be used to improve accuracy of prognostic classification, enabling the direction of personalized management.
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