Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study

Background Early diagnosis and treatment of esophageal squamous cell dysplasia (ESCdys) and esophageal squamous cell carcinoma (ESCC) could significantly reduce the incidence and mortality of ESCC. This pilot study aimed to investigate whether P16/CDKN2A methylation could serve as a cytologic biomar...

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Bibliographic Details
Published in:Cancer medicine (Malden, MA) MA), 2022-11, Vol.11 (21), p.4033-4042
Main Authors: Fan, Zhiyuan, Qin, Yu, Zhou, Jing, Chen, Ru, Gu, Jianhua, Li, Minjuan, Zhou, Jiachen, Li, Xinqing, Lin, Dongmei, Wang, Jinwu, Deng, Dajun, Wei, Wenqiang
Format: Article
Language:English
Subjects:
Alcohol
Biomarkers - metabolism
Biopsy
Carcinoma, Squamous Cell - diagnosis
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Cellular biology
Cytology
DNA Methylation
Dysplasia
early detection
Endoscopy
Esophageal cancer
Esophageal Neoplasms - diagnosis
Esophageal Neoplasms - genetics
Esophageal Neoplasms - metabolism
esophageal squamous cell carcinoma
Esophageal Squamous Cell Carcinoma - diagnosis
Esophageal Squamous Cell Carcinoma - genetics
Esophagus
Family medical history
Feasibility Studies
Genes, p16
Humans
Medical screening
minimally invasiveness
P16 methylation
p16 Protein
Pilot Projects
Prediction models
Regression analysis
Smoking
Squamous cell carcinoma
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Summary:Background Early diagnosis and treatment of esophageal squamous cell dysplasia (ESCdys) and esophageal squamous cell carcinoma (ESCC) could significantly reduce the incidence and mortality of ESCC. This pilot study aimed to investigate whether P16/CDKN2A methylation could serve as a cytologic biomarker for early detection of ESCdys and ESCC. Methods Paired esophageal biopsy and cytology specimens (exfoliated cells) were obtained from subjects at different stages of ESCC development. The methylation status of P16 gene in these two specimen types was determined using a 115‐bp MethyLight assay. Categorical data were compared by the Chi‐square test. Logistic regression was performed to assess adjusted odds ratios of P16 methylation associated with ESCC and ESCdys. Prediction models for identifying individuals at risk of ESCC and high‐grade ESCdys (high‐grade intraepithelial neoplasia, HGIN) were developed by multivariable logistic regression. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Internal validation of the prediction models was performed using the 1000‐bootstrap resample. Results A total of 105 subjects with diagnoses ranging from normal mucosa through ESCC were included in this study. An increase in P16 methylation frequency was observed with increasing severity of esophageal lesions (p for trend
ISSN:2045-7634
2045-7634
DOI:10.1002/cam4.4718