Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study
Abstract 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 cytolog...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-11-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.4718 |
| _version_ | 1811328207348039680 |
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| author | Zhiyuan Fan Yu Qin Jing Zhou Ru Chen Jianhua Gu Minjuan Li Jiachen Zhou Xinqing Li Dongmei Lin Jinwu Wang Dajun Deng Wenqiang Wei |
| author_facet | Zhiyuan Fan Yu Qin Jing Zhou Ru Chen Jianhua Gu Minjuan Li Jiachen Zhou Xinqing Li Dongmei Lin Jinwu Wang Dajun Deng Wenqiang Wei |
| author_sort | Zhiyuan Fan |
| collection | DOAJ |
| description | Abstract 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 <0.001). In the adjusted logistic regression models, P16 methylation in cytology specimens was positively associated with ESCC and ESCdys risk, whereas P16 methylation in biopsy specimens was only associated with a higher risk of developing ESCC. The predictive capacity of base model I (AUC, 0.816) for ESCC and HGIN was significantly increased by adding P16 methylation in cytology specimens (model III; AUC, 0.882; p = 0.043), but not P16 methylation in biopsy specimens (model II; AUC, 0.850; p = 0.225). Bootstrap validation showed optimism‐corrected AUC of 0.789 for model I, 0.822 for model II, and 0.854 for model III. Conclusion P16 methylation as a cytologic marker was associated with the ESCC development and has the potential for application in minimally invasive ESCC screening. |
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| id | doaj.art-608de1c95f42485c83b5f1192953cc60 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-13T15:21:08Z |
| publishDate | 2022-11-01 |
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| series | Cancer Medicine |
| spelling | doaj.art-608de1c95f42485c83b5f1192953cc602022-12-22T02:41:39ZengWileyCancer Medicine2045-76342022-11-0111214033404210.1002/cam4.4718Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot studyZhiyuan Fan0Yu Qin1Jing Zhou2Ru Chen3Jianhua Gu4Minjuan Li5Jiachen Zhou6Xinqing Li7Dongmei Lin8Jinwu Wang9Dajun Deng10Wenqiang Wei11Office of 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 ChinaOffice of 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 ChinaKey Laboratory of Carcinogenesis and Translational Research (MOE/Beijing), Division of Etiology Peking University Cancer Hospital and Institute Beijing ChinaOffice of 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 ChinaOffice of 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 ChinaOffice of 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 ChinaDepartment of Epidemiology and Biostatistics, School of Public Health Xi'an Jiaotong University Health Science Center Xi'an ChinaOffice of 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 ChinaDepartment of Pathology Peking University Cancer Hospital Beijing ChinaDepartment of Pathology Linzhou Cancer Hospital Linzhou ChinaKey Laboratory of Carcinogenesis and Translational Research (MOE/Beijing), Division of Etiology Peking University Cancer Hospital and Institute Beijing ChinaOffice of 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 ChinaAbstract 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 <0.001). In the adjusted logistic regression models, P16 methylation in cytology specimens was positively associated with ESCC and ESCdys risk, whereas P16 methylation in biopsy specimens was only associated with a higher risk of developing ESCC. The predictive capacity of base model I (AUC, 0.816) for ESCC and HGIN was significantly increased by adding P16 methylation in cytology specimens (model III; AUC, 0.882; p = 0.043), but not P16 methylation in biopsy specimens (model II; AUC, 0.850; p = 0.225). Bootstrap validation showed optimism‐corrected AUC of 0.789 for model I, 0.822 for model II, and 0.854 for model III. Conclusion P16 methylation as a cytologic marker was associated with the ESCC development and has the potential for application in minimally invasive ESCC screening.https://doi.org/10.1002/cam4.4718cytologyearly detectionesophageal squamous cell carcinomaminimally invasivenessP16 methylation |
| spellingShingle | Zhiyuan Fan Yu Qin Jing Zhou Ru Chen Jianhua Gu Minjuan Li Jiachen Zhou Xinqing Li Dongmei Lin Jinwu Wang Dajun Deng Wenqiang Wei Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study Cancer Medicine cytology early detection esophageal squamous cell carcinoma minimally invasiveness P16 methylation |
| title | Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study |
| title_full | Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study |
| title_fullStr | Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study |
| title_full_unstemmed | Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study |
| title_short | Feasibility of using P16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening: A pilot study |
| title_sort | feasibility of using p16 methylation as a cytologic marker for esophageal squamous cell carcinoma screening a pilot study |
| topic | cytology early detection esophageal squamous cell carcinoma minimally invasiveness P16 methylation |
| url | https://doi.org/10.1002/cam4.4718 |
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