Copy Number Alterations Predict Development of OSCC from Oral Leukoplakia

X Cai; J Zhang; L Li; L Liu; M Tang; X Zhou; C Peng; X Li; X Chen; M Xu; H Zhang; J Wang; Y Huang; T Li

doi:10.1177/00220345231217160

Copy Number Alterations Predict Development of OSCC from Oral Leukoplakia

J Dent Res. 2024 Feb;103(2):138-146. doi: 10.1177/00220345231217160. Epub 2024 Jan 12.

Authors

X Cai^{1

2}, J Zhang^{1

2}, L Li³, L Liu⁴, M Tang⁵, X Zhou^{1

2}, C Peng^{1

2}, X Li⁶, X Chen⁷, M Xu⁷, H Zhang⁸, J Wang⁹, Y Huang^{5

10}, T Li^{1

2

11}

Affiliations

¹ Department of Oral Pathology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
² Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions, Chinese Academy of Medical Sciences (2019RU034), Beijing, China.
³ Hunan Key Laboratory of Oral Health Research & Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Changsha, Hunan, China.
⁴ Changping Laboratory, Beijing, China.
⁵ Beijing Advanced Innovation Center for Genomics (ICG), Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, China.
⁶ Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
⁷ Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
⁸ Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
⁹ School of Life Sciences, Tsinghua University, Beijing, China, Tsinghua University, Beijing, China.
¹⁰ College of Chemistry and Molecular Engineering and Beijing National Laboratory for Molecular Sciences, Peking University, Beijing, China.
¹¹ Laboratory of Oral Biomedicine, Henan University School of Stomatology, Kaifeng, Henan, China.

PMID: 38217281
DOI: 10.1177/00220345231217160

Abstract

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 score^high group showed an increased risk of malignant transformation than the CNA score^low 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.

Keywords: biomarker; dysplasia; genomic alteration; hyperplasia; malignant transformation; oral squamous cell carcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Carcinoma, Squamous Cell* / genetics
Carcinoma, Squamous Cell* / pathology
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / pathology
DNA Copy Number Variations / genetics
Head and Neck Neoplasms*
Humans
Hyperplasia
Leukoplakia, Oral / genetics
Leukoplakia, Oral / pathology
Mouth Neoplasms* / genetics
Mouth Neoplasms* / pathology
Squamous Cell Carcinoma of Head and Neck

Substances

Biomarkers