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Quantification of somatic copy-number alterations to predict malignant transformation of oral leukoplakia: A
Zirui Wang1, Wentao Wu1, Yanlu Xu1
1Department of Oral Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China.
Objective:
This study aimed to evaluate the predictive value of a quantitative index measuring the extent of somatic copy-number alteration (SCNA) for malignant transformation (MT) in oral leukoplakia (OLK).
Methods:
A prospective cohort of 122 patients with OLK was followed for a median of 74 months. Whole-exome sequencing (WES) was performed on fresh-frozen tissue specimens. SCNA-L was defined as the total autosomal length of segments exceeding predefined copy-number and minimum-width thresholds. The cohort was stratified into high- and low-SCNA-L groups using a median cutoff of 3.3. The primary outcome was MT to oral squamous cell carcinoma (OSCC). Statistical analyses included Kaplan-Meier survival analysis, Cox proportional hazards models, time-dependent ROC curves, a 1,000-resample bootstrap optimism-corrected C-index, and bootstrap internal validation using calibration curves.
Results:
The MT rate was significantly higher in the high-SCNA-L group (26.7%) than in the low-SCNA-L group (6.5%; P < 0.01). SCNA-L remained an independent predictor of MT in the multivariable analysis (hazard ratio = 4.684, P = 0.006). The predictive model, incorporating SCNA-L and lesion type, demonstrated adequate discrimination and satisfactory calibration for mid-term prediction.
Conclusions:
As an independent predictor of MT in OLK, the quantitative index SCNA-L can serve as a molecular supplement to conventional pathological grading.
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