@article{0ac9df048f24483e9a8477353747fdca,
title = "Validation of SCT methylation as a hallmark biomarker for lung cancers",
abstract = "Introduction: The human secretin gene (SCT) encodes secretin, a hormone with limited tissue distribution. Analysis of the 450k methylation array data in The Cancer Genome Atlas (TCGA) indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential biomarker for lung cancer. Methods: We analyzed data from TCGA and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation-specific polymerase chain reaction assays. Results: The analyses of TCGA 450K data for 801 samples showed that SCT hypermethylation has an area under the curve (AUC) value greater than 0.98 that can be used to distinguish lung adenocarcinomas or squamous cell carcinomas from nonmalignant lung tissue. Bisulfite sequencing of lung cancer cell lines and normal blood cells allowed us to confirm that SCT methylation is highly discriminative. By applying a quantitative methylation-specific polymerase chain reaction assay, we found that SCT hypermethylation is frequently detected in all major subtypes of malignant non- small cell lung cancer (AUC = 0.92, n = 108) and small cell lung cancer (AUC = 0.93, n = 40) but is less frequent in lung carcinoids (AUC = 0.54, n = 20). SCT hypermethylation appeared in samples of lung carcinoma in situ during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450k data showed that SCT hypermethylation is highly discriminative in most other types of malignant tumors but less frequent in low-grade malignant tumors. The only normal tissue with a high level of methylation was the placenta. Conclusions: Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, is less frequent in low-grade malignant tumors (including lung carcinoids), and appears at the carcinoma in situ stage.",
keywords = "Cancer biomarker, FFPE DNA SCT qMSP, Lung cancer, SCT methylation, Secretin",
author = "Zhang, {Yu An} and Xiaotu Ma and Adwait Sathe and Junya Fujimoto and Wistuba, {Ignacio I.} and Stephen Lam and Yasushi Yatabe and Wang, {Yi Wei} and Victor Stastny and Boning Gao and Larsen, {Jill E.} and Luc Girard and Xiaoyun Liu and Kai Song and Carmen Behrens and Neda Kalhor and Yang Xie and Zhang, {Michael Q.} and Minna, {John D.} and Gazdar, {Adi F.}",
note = "Funding Information: Disclosure: Dr. M. Q. Zhang was supported by National Institutes of Health grant HG001696 , National Basic Research Program of China grant 2012CB316503 , and National Natural Science Foundation of China grants 91019016 and 31061160497 . The remaining authors declare no conflict of interest. Funding Information: Partial funding was provided by the Texas Specialized Program of Research Excellence in Lung Cancer ( P50CA70907 ) and the Early Detection Research Network ( U01CA084971 ), National Cancer Institute and the Canary Foundation (Palo Alto, CA), and a grant ( LC090634 ) from the U.S. Army Lung Cancer Research Program . The authors thank Rachael Essman for her assistance with bisulfite DNA sequencing and data analysis, Drs. Holcomb Thomas and David Shames (Genentech, South San Francisco, CA) for their generous sharing their RNase P reference PCR assay primers and probe sequences, and Sukhinder Khattra (British Columbia Cancer Research Center, Vancouver, Canada) for kind assistance in obtaining multistage FFPE samples for lung SCCs. Funding Information: Partial funding was provided by the Texas Specialized Program of Research Excellence in Lung Cancer (P50CA70907) and the Early Detection Research Network (U01CA084971), National Cancer Institute and the Canary Foundation (Palo Alto, CA), and a grant (LC090634) from the U.S. Army Lung Cancer Research Program. The authors thank Rachael Essman for her assistance with bisulfite DNA sequencing and data analysis, Drs. Holcomb Thomas and David Shames (Genentech, South San Francisco, CA) for their generous sharing their RNase P reference PCR assay primers and probe sequences, and Sukhinder Khattra (British Columbia Cancer Research Center, Vancouver, Canada) for kind assistance in obtaining multistage FFPE samples for lung SCCs. Publisher Copyright: {\textcopyright} 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.",
year = "2016",
month = mar,
day = "23",
doi = "10.1016/j.jtho.2015.11.004",
language = "English (US)",
volume = "11",
pages = "346--360",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",
number = "3",
}