Somatic CDKN2A copy number variations are associated with the prognosis of esophageal squamous cell dysplasia

Background: Somatic copy number variations (SCNVs) in theCDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whetherCDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value ofCDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys.Methods: This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detectCDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models.Results: A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in theCDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69]vs. 35.0% [28/80]vs. 51.8% [29/56],P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower (P = 0.008), while the cumulative progression rate was higher (P = 0.017) in ESCdys patients withCDKN2A deletion than in those withoutCDKN2A deletion.CDKN2A deletion was also an independent predictor of prognosis in ESCdys (P = 0.004) in the multivariable analysis.Conclusion: The results indicated thatCDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.