Fan Zhiyuan, Zhou Jing, Tian Yuan, Qin Yu, Liu Zhaojun, Gu Liankun, Dawsey Sanford M, Wei Wenqiang, Deng Dajun
National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Key Laboratory of Carcinogenesis and Translational Research (MOE/Beijing), Division of Etiology, Peking University Cancer Hospital and Institute, Beijing 100142, China.
Chin Med J (Engl). 2024 Apr 20;137(8):980-989. doi: 10.1097/CM9.0000000000002982. Epub 2024 Mar 6.
Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A 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 of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys.
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 detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models.
A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A 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 with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys ( P = 0.004) in the multivariable analysis.
The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.
CDKN2A基因的体细胞拷贝数变异（SCNV）是食管鳞状细胞癌发育异常-癌序列中最常见的事件之一。然而，CDKN2A SCNV是否为食管鳞状上皮发育异常（ESCdys）患者的风险分层和管理的有用生物标志物尚不清楚。本研究旨在探讨轻度或中度（m/M）ESCdys患者中CDKN2A SCNV的特征及预后价值。
本研究对2005年至2019年期间在中国五个高危地区（河北省磁县、四川省盐亭县、河南省林州市、江苏省扬中市和山东省肥城市）基线诊断为m/M ESCdys的205例患者进行了一项前瞻性多中心研究。从患者的石蜡活检样本和配对的外周血白细胞中提取基因组DNA，并使用定量聚合酶链反应检测法P16-Light检测CDKN2A拷贝数。使用竞争风险模型评估ESCdys的累积消退率和进展率。
共纳入205例基线m/M ESCdys患者。CDKN2A缺失队列中ESCdys消退的比例显著低于二倍体和扩增队列（18.8%[13/69]对35.0%[28/80]对51.8%[29/56]，P<0.001）。在单变量竞争风险分析中，CDKN2A缺失的ESCdys患者的累积消退率在统计学上显著较低（P = 0.008），而累积进展率较高（P = 0.017）。在多变量分析中，CDKN2A缺失也是ESCdys预后的独立预测因素（P = 0.004）。
结果表明，CDKN2A SCNV与ESCdys的预后相关，可能作为风险分层的潜在生物标志物。
