Accurate Nonendoscopic Detection of Esophageal Squamous Cell Carcinoma Using Methylated DNA Biomarkers

Ke Ma¹, Andrew Kalra¹, Hua-Ling Tsai², Samson Okello³, Yulan Cheng¹, Stephen J Meltzer⁴; Esophageal Squamous Cell Carcinoma Consortium

Collaborators, Affiliations

Collaborators

Esophageal Squamous Cell Carcinoma Consortium:
Boniface A E Lumori³, Christopher K Opio⁵, Simran Jit¹, Ludmila Danilova², Zhe Wang⁶, Cem Simsek¹, Saowanee Ngamruengphong¹, Eun Ji Shin¹, Mouen A Khashab¹, Vikesh K Singh¹, Alan H Tieu¹, Corey Nolet⁷, Dennis Gong⁸, Kai-Hua Chang⁹, Vishnu Prasath⁹, Robert C Bollinger¹⁰, Tza-Huei Wang¹¹, Josephine Feliciano¹², Vincent K Lam¹², Richard Battafarano¹⁰, Michelle Turner¹², Peggy Lang¹², Kristen A Marrone¹², Hao Wang⁵

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
² Division of Biostatistics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
³ Department of Internal Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
⁴ Division of Gastroenterology and Hepatology, Department of Medicine and, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: smeltzer@jhmi.edu.
⁵ Department of Internal Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
⁶ Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Gastroenterology, Tongji University School of Medicine, Shanghai, China.
⁷ Capsulomics, Inc., Baltimore, Maryland.
⁸ Capsulomics, Inc., Baltimore, Maryland; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
⁹ Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹⁰ Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹¹ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
¹² Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.

PMID: 35483446
PMCID: PMC9555873
DOI: 10.1053/j.gastro.2022.04.021

Accurate Nonendoscopic Detection of Esophageal Squamous Cell Carcinoma Using Methylated DNA Biomarkers

Ke Ma et al. Gastroenterology. 2022 Aug.

. 2022 Aug;163(2):507-509.e2.

doi: 10.1053/j.gastro.2022.04.021. Epub 2022 Apr 26.

Authors

Ke Ma¹, Andrew Kalra¹, Hua-Ling Tsai², Samson Okello³, Yulan Cheng¹, Stephen J Meltzer⁴; Esophageal Squamous Cell Carcinoma Consortium

Collaborators

Esophageal Squamous Cell Carcinoma Consortium:
Boniface A E Lumori³, Christopher K Opio⁵, Simran Jit¹, Ludmila Danilova², Zhe Wang⁶, Cem Simsek¹, Saowanee Ngamruengphong¹, Eun Ji Shin¹, Mouen A Khashab¹, Vikesh K Singh¹, Alan H Tieu¹, Corey Nolet⁷, Dennis Gong⁸, Kai-Hua Chang⁹, Vishnu Prasath⁹, Robert C Bollinger¹⁰, Tza-Huei Wang¹¹, Josephine Feliciano¹², Vincent K Lam¹², Richard Battafarano¹⁰, Michelle Turner¹², Peggy Lang¹², Kristen A Marrone¹², Hao Wang⁵

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
² Division of Biostatistics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
³ Department of Internal Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
⁴ Division of Gastroenterology and Hepatology, Department of Medicine and, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: smeltzer@jhmi.edu.
⁵ Department of Internal Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
⁶ Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Gastroenterology, Tongji University School of Medicine, Shanghai, China.
⁷ Capsulomics, Inc., Baltimore, Maryland.
⁸ Capsulomics, Inc., Baltimore, Maryland; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
⁹ Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹⁰ Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
¹¹ Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
¹² Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.

PMID: 35483446
PMCID: PMC9555873
DOI: 10.1053/j.gastro.2022.04.021

No abstract available

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Figures

**Figure 1.**
(A) Comparison of methylation levels between control and esophageal squamous cell carcinoma (ESCC) samples collected via the sponge device in the training set. Sample DNA was collected via the retrievable esophageal sponge device. Horizontal lines represent median methylation index values with 95% CI. *cg20655070* (P = 0.004), *SLC35F1* (P < 0.001), *TAC1* (P = 0.001), *ZNF132* (P < 0.001), and *ZNF542* (P = 0.001) methylation levels were significantly higher in cytologic DNA of ESCC patients vs patients without neoplastic disease. (B) Univariate ROC analysis of diagnostic performance of *cg20655070*, *SLC35F1*, *TAC1*, *ZNF132*, and *ZNF542* in DNA collected with the retrievable esophageal sponge capsule in the training set. The scores generated from the classification algorithm, as indicated by the dark blue plot labeled “Selected” (*cg20655070* + *SLC35F1* + *ZNF132* + *age*), represent the weighted combination of biomarkers and clinical variables as identified by the LASSO approach with 5-fold cross-validation. The *red square* corresponds to Youden’s point and represents the optimum combination of sensitivity (0.86) and specificity (0.86) in the training set data.

See this image and copyright information in PMC

References

1. Sung H, et al. CA Cancer J Clin 2021;71:209–249. - PubMed
1. Couch G, et al. Cancer Prev Res 2016;9:558–566. - PMC - PubMed
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1. Moinova HR, et al. Sci Transl Med 2018;10. - PMC - PubMed
1. Iyer PG, et al. Am J Gastroenterol 2018;113:1156–1166. - PubMed

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Accurate Nonendoscopic Detection of Esophageal Squamous Cell Carcinoma Using Methylated DNA Biomarkers

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Accurate Nonendoscopic Detection of Esophageal Squamous Cell Carcinoma Using Methylated DNA Biomarkers

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