Copy Number Alterations Predict Development of OSCC from Oral Leukoplakia
Oral leukoplakia (OLK) is a common type of potentially malignant disorder. Early identification of the malignancy potential leads to a better management of OLK and prediction of development of oral squamous cell carcinoma (OSCC). However, there has been no effective biomarker to assess the risk of malignancy in OLK. Genomic copy number alteration (CNA) is a complex chromosomal structural variation in the genome and has been identified as a potential biomarker in multiple cancers. This study aimed to develop a predictive model for the malignant transformation risk of OLK by copy number analysis. A total of 431 OLK samples with long-term follow-up (median follow-up of 67 mo) from multiple academic centers were analyzed for CNAs. CNA events increased with the severity of hyperplasia, mild dysplasia, moderate dysplasia, and severe dysplasia. More CNA events were present in patients with OLK who later developed OSCC than in those with OLK who did not. By multivariate Cox regression analysis, the OLK of the CNA scorehigh group showed an increased risk of malignant transformation than the CNA scorelow group (P < 0.001). A CNA score model was developed to accurately predict the prognosis (area under the receiver operating characteristic curve [AUC] = 0.879; 95% confidence interval [CI], 0.799-0.959) and was validated using data from 2 external centers (AUC = 0.836, 95% CI, 0.683-0.989; AUC = 0.876, 95% CI, 0.682-1.000), and all of them showed better prediction performances than histopathological grade in assessing the transformation risk of OLK. Furthermore, we performed CNA models among 4 subgroups of OLK with hyperplasia, mild dysplasia, moderate dysplasia, and severe dysplasia and found that CNA score can accurately predict malignant transformation of different subgroups. CNA score may be a useful biomarker to predict malignant transformation of OLK. Subtyping of OLK by the CNA score could contribute to better management of OLK and predicting development of OSCC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:103 |
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| Enthalten in: |
Journal of dental research - 103(2024), 2 vom: 20. Feb., Seite 138-146 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cai, X [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarker |
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| Anmerkungen: |
Date Completed 06.02.2024 Date Revised 21.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1177/00220345231217160 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367078295 |
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| 245 | 1 | 0 | |a Copy Number Alterations Predict Development of OSCC from Oral Leukoplakia |
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| 520 | |a Oral leukoplakia (OLK) is a common type of potentially malignant disorder. Early identification of the malignancy potential leads to a better management of OLK and prediction of development of oral squamous cell carcinoma (OSCC). However, there has been no effective biomarker to assess the risk of malignancy in OLK. Genomic copy number alteration (CNA) is a complex chromosomal structural variation in the genome and has been identified as a potential biomarker in multiple cancers. This study aimed to develop a predictive model for the malignant transformation risk of OLK by copy number analysis. A total of 431 OLK samples with long-term follow-up (median follow-up of 67 mo) from multiple academic centers were analyzed for CNAs. CNA events increased with the severity of hyperplasia, mild dysplasia, moderate dysplasia, and severe dysplasia. More CNA events were present in patients with OLK who later developed OSCC than in those with OLK who did not. By multivariate Cox regression analysis, the OLK of the CNA scorehigh group showed an increased risk of malignant transformation than the CNA scorelow group (P < 0.001). A CNA score model was developed to accurately predict the prognosis (area under the receiver operating characteristic curve [AUC] = 0.879; 95% confidence interval [CI], 0.799-0.959) and was validated using data from 2 external centers (AUC = 0.836, 95% CI, 0.683-0.989; AUC = 0.876, 95% CI, 0.682-1.000), and all of them showed better prediction performances than histopathological grade in assessing the transformation risk of OLK. Furthermore, we performed CNA models among 4 subgroups of OLK with hyperplasia, mild dysplasia, moderate dysplasia, and severe dysplasia and found that CNA score can accurately predict malignant transformation of different subgroups. CNA score may be a useful biomarker to predict malignant transformation of OLK. Subtyping of OLK by the CNA score could contribute to better management of OLK and predicting development of OSCC | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a biomarker | |
| 650 | 4 | |a dysplasia | |
| 650 | 4 | |a genomic alteration | |
| 650 | 4 | |a hyperplasia | |
| 650 | 4 | |a malignant transformation | |
| 650 | 4 | |a oral squamous cell carcinoma | |
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| 700 | 1 | |a Liu, L |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, M |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, X |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, C |e verfasserin |4 aut | |
| 700 | 1 | |a Li, X |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, X |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, M |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, H |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, J |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Y |e verfasserin |4 aut | |
| 700 | 1 | |a Li, T |e verfasserin |4 aut | |
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