Validation of SCT methylation as a hallmark biomarker for lung cancers

Yu An Zhang, Xiaotu Ma, Adwait Sathe, Junya Fujimoto, Ignacio I. Wistuba, Stephen Lam, Yasushi Yatabe, Yi Wei Wang, Victor Stastny, Boning Gao, Jill E. Larsen, Luc Girard, Xiaoyun Liu, Kai Song, Carmen Behrens, Neda Kalhor, Yang Xie, Michael Q. Zhang, John D. Minna, Adi F. Gazdar

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)346-360
Number of pages15
JournalJournal of Thoracic Oncology
Volume11
Issue number3
DOIs
StatePublished - Mar 23 2016

Fingerprint

Secretin
Methylation
Lung Neoplasms
Biomarkers
Genes
Atlases
Area Under Curve
Neoplasms
Lung
Genome
Carcinoma in Situ
Carcinoid Tumor
Polymerase Chain Reaction
Small Cell Lung Carcinoma
Tissue Distribution
DNA Sequence Analysis
Genetic Promoter Regions
Non-Small Cell Lung Carcinoma
Placenta
Squamous Cell Carcinoma

Keywords

  • Cancer biomarker
  • FFPE DNA SCT qMSP
  • Lung cancer
  • SCT methylation
  • Secretin

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Zhang, Y. A., Ma, X., Sathe, A., Fujimoto, J., Wistuba, I. I., Lam, S., ... Gazdar, A. F. (2016). Validation of SCT methylation as a hallmark biomarker for lung cancers. Journal of Thoracic Oncology, 11(3), 346-360. https://doi.org/10.1016/j.jtho.2015.11.004

Validation of SCT methylation as a hallmark biomarker for lung cancers. / Zhang, Yu An; Ma, Xiaotu; Sathe, Adwait; Fujimoto, Junya; Wistuba, Ignacio I.; Lam, Stephen; Yatabe, Yasushi; Wang, Yi Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E.; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q.; Minna, John D.; Gazdar, Adi F.

In: Journal of Thoracic Oncology, Vol. 11, No. 3, 23.03.2016, p. 346-360.

Research output: Contribution to journalArticle

Zhang, YA, Ma, X, Sathe, A, Fujimoto, J, Wistuba, II, Lam, S, Yatabe, Y, Wang, YW, Stastny, V, Gao, B, Larsen, JE, Girard, L, Liu, X, Song, K, Behrens, C, Kalhor, N, Xie, Y, Zhang, MQ, Minna, JD & Gazdar, AF 2016, 'Validation of SCT methylation as a hallmark biomarker for lung cancers', Journal of Thoracic Oncology, vol. 11, no. 3, pp. 346-360. https://doi.org/10.1016/j.jtho.2015.11.004
Zhang, Yu An ; Ma, Xiaotu ; Sathe, Adwait ; Fujimoto, Junya ; Wistuba, Ignacio I. ; Lam, Stephen ; Yatabe, Yasushi ; Wang, Yi Wei ; Stastny, Victor ; Gao, Boning ; Larsen, Jill E. ; Girard, Luc ; Liu, Xiaoyun ; Song, Kai ; Behrens, Carmen ; Kalhor, Neda ; Xie, Yang ; Zhang, Michael Q. ; Minna, John D. ; Gazdar, Adi F. / Validation of SCT methylation as a hallmark biomarker for lung cancers. In: Journal of Thoracic Oncology. 2016 ; Vol. 11, No. 3. pp. 346-360.
@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.}",
year = "2016",
month = "3",
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",

}

TY - JOUR

T1 - Validation of SCT methylation as a hallmark biomarker for lung cancers

AU - Zhang, Yu An

AU - Ma, Xiaotu

AU - Sathe, Adwait

AU - Fujimoto, Junya

AU - Wistuba, Ignacio I.

AU - Lam, Stephen

AU - Yatabe, Yasushi

AU - Wang, Yi Wei

AU - Stastny, Victor

AU - Gao, Boning

AU - Larsen, Jill E.

AU - Girard, Luc

AU - Liu, Xiaoyun

AU - Song, Kai

AU - Behrens, Carmen

AU - Kalhor, Neda

AU - Xie, Yang

AU - Zhang, Michael Q.

AU - Minna, John D.

AU - Gazdar, Adi F.

PY - 2016/3/23

Y1 - 2016/3/23

N2 - 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.

AB - 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.

KW - Cancer biomarker

KW - FFPE DNA SCT qMSP

KW - Lung cancer

KW - SCT methylation

KW - Secretin

UR - http://www.scopus.com/inward/record.url?scp=84962621516&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962621516&partnerID=8YFLogxK

U2 - 10.1016/j.jtho.2015.11.004

DO - 10.1016/j.jtho.2015.11.004

M3 - Article

C2 - 26725182

AN - SCOPUS:84962621516

VL - 11

SP - 346

EP - 360

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

IS - 3

ER -