Performance of DNA-based biomarkers for classification of adrenocortical carcinoma : a prognostic study
© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology..
OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare aggressive malignancy with heterogeneous clinical outcomes. Recent studies proposed a combination of clinical/histopathological parameters (S-GRAS score) or molecular biomarkers (BMs) to improve prognostication. We performed a comparative analysis of DNA-based BMs by evaluating their added prognostic value to the S-GRAS score.
DESIGN AND METHODS: A total of 194 formalin-fixed, paraffin-embedded (FFPE) ACC samples were analysed, including a retrospective training cohort (n = 107) and a prospective validation cohort (n = 87). Targeted DNA sequencing and pyrosequencing were used to detect somatic single-nucleotide variations in ACC-specific genes and methylation in the promoter region of paired box 5 (PAX5). The European Network for the Study of Adrenocortical Tumors (ENSAT) tumour stage, age, symptoms at presentation, resection status, and Ki-67 were combined to calculate S-GRAS. Endpoints were overall (OS), progression-free (PFS), and disease-free survival (DFS). Prognostic role was evaluated by multivariable survival analysis and their performance compared by Harrell's concordance index (C index).
RESULTS: In training cohort, an independent prognostic role was confirmed at multivariate analysis for two DNA-based BMs: alterations in Wnt/β-catenin and Rb/p53 pathways and hypermethylated PAX5 (both P< .05 for PFS and DFS, hazard ratio [HR] 1.47-2.33). These were combined to S-GRAS to obtain a combined (COMBI) score. At comparative analysis, the best discriminative prognostic model was COMBI score in both cohorts for all endpoints, followed by S-GRAS score (C index for OS 0.724 and 0.765, PFS 0.717 and 0.670, and DFS 0.699 and 0.644, respectively).
CONCLUSIONS: Targeted DNA-based BM evaluated on routinely available FFPE samples improves prognostication of ACC beyond routinely available clinical and histopathological parameters. This approach may help to better individualise patient's management.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:189 |
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| Enthalten in: |
European journal of endocrinology - 189(2023), 2 vom: 02. Aug., Seite 262-270 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lippert, Juliane [VerfasserIn] |
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| Links: |
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| Themen: |
Adrenal cancer |
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| Anmerkungen: |
Date Completed 31.08.2023 Date Revised 31.08.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/ejendo/lvad112 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360898815 |
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| 100 | 1 | |a Lippert, Juliane |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Performance of DNA-based biomarkers for classification of adrenocortical carcinoma |b a prognostic study |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. | ||
| 520 | |a OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare aggressive malignancy with heterogeneous clinical outcomes. Recent studies proposed a combination of clinical/histopathological parameters (S-GRAS score) or molecular biomarkers (BMs) to improve prognostication. We performed a comparative analysis of DNA-based BMs by evaluating their added prognostic value to the S-GRAS score | ||
| 520 | |a DESIGN AND METHODS: A total of 194 formalin-fixed, paraffin-embedded (FFPE) ACC samples were analysed, including a retrospective training cohort (n = 107) and a prospective validation cohort (n = 87). Targeted DNA sequencing and pyrosequencing were used to detect somatic single-nucleotide variations in ACC-specific genes and methylation in the promoter region of paired box 5 (PAX5). The European Network for the Study of Adrenocortical Tumors (ENSAT) tumour stage, age, symptoms at presentation, resection status, and Ki-67 were combined to calculate S-GRAS. Endpoints were overall (OS), progression-free (PFS), and disease-free survival (DFS). Prognostic role was evaluated by multivariable survival analysis and their performance compared by Harrell's concordance index (C index) | ||
| 520 | |a RESULTS: In training cohort, an independent prognostic role was confirmed at multivariate analysis for two DNA-based BMs: alterations in Wnt/β-catenin and Rb/p53 pathways and hypermethylated PAX5 (both P< .05 for PFS and DFS, hazard ratio [HR] 1.47-2.33). These were combined to S-GRAS to obtain a combined (COMBI) score. At comparative analysis, the best discriminative prognostic model was COMBI score in both cohorts for all endpoints, followed by S-GRAS score (C index for OS 0.724 and 0.765, PFS 0.717 and 0.670, and DFS 0.699 and 0.644, respectively) | ||
| 520 | |a CONCLUSIONS: Targeted DNA-based BM evaluated on routinely available FFPE samples improves prognostication of ACC beyond routinely available clinical and histopathological parameters. This approach may help to better individualise patient's management | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a adrenal cancer | |
| 650 | 4 | |a molecular oncology | |
| 650 | 4 | |a personalised medicine | |
| 650 | 4 | |a prognosis | |
| 700 | 1 | |a Dischinger, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Appenzeller, Silke |e verfasserin |4 aut | |
| 700 | 1 | |a Prete, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a Kircher, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Skordilis, Kassiani |e verfasserin |4 aut | |
| 700 | 1 | |a Elhassan, Yasir S |e verfasserin |4 aut | |
| 700 | 1 | |a Altieri, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Fassnacht, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Ronchi, Cristina L |e verfasserin |4 aut | |
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