ITPKA gene body methylation regulates gene expression and serves as an early diagnostic marker in lung and other cancers

Yi Wei Wang, Xiaotu Ma, Yu An Zhang, Mei Jung Wang, Yasushi Yatabe, Stephen Lam, Luc Girard, Jeou Yuan Chen, Adi F. Gazdar

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Introduction: Despite recent advances in cancer therapy, the overall 5-year survival rate of patients with lung cancer remains low. The aim of our study was to search for novel markers for early diagnosis in patients with lung cancer. Methods: Complementary DNA microarray analysis was performed in primary lung adenocarcinomas and cell lines to search for differentially expressed genes, followed by in vivo and in vitro tumorigenic assays to characterize the oncogenic potential of the candidate genes. Gene body methylation was analyzed by 450K methylation array, bisulfite sequencing, and quantitative methylation-specific polymerase chain reaction assays. In silico analysis of The Cancer Genome Atlas data set was also performed. Results: Inositol-Trisphosphate 3-kinase A gene (ITPKA), a kinase with limited tissue distribution, was identified as a potential oncogene. We showed that ITPKA expression is up-regulated in many forms of cancers, including lung and breast cancers, and that overexpressed ITPKA contributes to tumorigenesis. We also demonstrated that ITPKA expression is regulated by epigenetic DNA methylation of ITPKA gene body through modulation of the binding of SP1 transcription factor to the ITPKA promoter. ITPKA gene body displayed low or absent levels of methylation in most normal tissue but was significantly methylated in malignant tumors. In lung cancer, ITPKA gene body methylation first appeared at the in situ carcinoma stage and progressively increased after invasion. Conclusions: ITPKA is a potential oncogene that it is overexpressed in most tumors, and its overexpression promotes tumorigenesis. ITPKA gene body methylation regulates its expression and thus serves as a novel and potential biomarker for early cancer detection.

Original languageEnglish (US)
Pages (from-to)1469-1481
Number of pages13
JournalJournal of Thoracic Oncology
Volume11
Issue number9
DOIs
StatePublished - 2016

Fingerprint

Inositol
Methylation
Lung Neoplasms
Phosphotransferases
Gene Expression
Genes
Oncogenes
Neoplasms
Carcinogenesis
Breast Neoplasms
Atlases
Carcinoma in Situ
Tissue Distribution
DNA Methylation
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Early Detection of Cancer
Epigenomics
Computer Simulation
Early Diagnosis

Keywords

  • Biomarker
  • Gene body methylation
  • Itpka
  • Oncogene
  • Sp1

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

ITPKA gene body methylation regulates gene expression and serves as an early diagnostic marker in lung and other cancers. / Wang, Yi Wei; Ma, Xiaotu; Zhang, Yu An; Wang, Mei Jung; Yatabe, Yasushi; Lam, Stephen; Girard, Luc; Chen, Jeou Yuan; Gazdar, Adi F.

In: Journal of Thoracic Oncology, Vol. 11, No. 9, 2016, p. 1469-1481.

Research output: Contribution to journalArticle

Wang, Yi Wei ; Ma, Xiaotu ; Zhang, Yu An ; Wang, Mei Jung ; Yatabe, Yasushi ; Lam, Stephen ; Girard, Luc ; Chen, Jeou Yuan ; Gazdar, Adi F. / ITPKA gene body methylation regulates gene expression and serves as an early diagnostic marker in lung and other cancers. In: Journal of Thoracic Oncology. 2016 ; Vol. 11, No. 9. pp. 1469-1481.
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abstract = "Introduction: Despite recent advances in cancer therapy, the overall 5-year survival rate of patients with lung cancer remains low. The aim of our study was to search for novel markers for early diagnosis in patients with lung cancer. Methods: Complementary DNA microarray analysis was performed in primary lung adenocarcinomas and cell lines to search for differentially expressed genes, followed by in vivo and in vitro tumorigenic assays to characterize the oncogenic potential of the candidate genes. Gene body methylation was analyzed by 450K methylation array, bisulfite sequencing, and quantitative methylation-specific polymerase chain reaction assays. In silico analysis of The Cancer Genome Atlas data set was also performed. Results: Inositol-Trisphosphate 3-kinase A gene (ITPKA), a kinase with limited tissue distribution, was identified as a potential oncogene. We showed that ITPKA expression is up-regulated in many forms of cancers, including lung and breast cancers, and that overexpressed ITPKA contributes to tumorigenesis. We also demonstrated that ITPKA expression is regulated by epigenetic DNA methylation of ITPKA gene body through modulation of the binding of SP1 transcription factor to the ITPKA promoter. ITPKA gene body displayed low or absent levels of methylation in most normal tissue but was significantly methylated in malignant tumors. In lung cancer, ITPKA gene body methylation first appeared at the in situ carcinoma stage and progressively increased after invasion. Conclusions: ITPKA is a potential oncogene that it is overexpressed in most tumors, and its overexpression promotes tumorigenesis. ITPKA gene body methylation regulates its expression and thus serves as a novel and potential biomarker for early cancer detection.",
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AU - Wang, Yi Wei

AU - Ma, Xiaotu

AU - Zhang, Yu An

AU - Wang, Mei Jung

AU - Yatabe, Yasushi

AU - Lam, Stephen

AU - Girard, Luc

AU - Chen, Jeou Yuan

AU - Gazdar, Adi F.

PY - 2016

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N2 - Introduction: Despite recent advances in cancer therapy, the overall 5-year survival rate of patients with lung cancer remains low. The aim of our study was to search for novel markers for early diagnosis in patients with lung cancer. Methods: Complementary DNA microarray analysis was performed in primary lung adenocarcinomas and cell lines to search for differentially expressed genes, followed by in vivo and in vitro tumorigenic assays to characterize the oncogenic potential of the candidate genes. Gene body methylation was analyzed by 450K methylation array, bisulfite sequencing, and quantitative methylation-specific polymerase chain reaction assays. In silico analysis of The Cancer Genome Atlas data set was also performed. Results: Inositol-Trisphosphate 3-kinase A gene (ITPKA), a kinase with limited tissue distribution, was identified as a potential oncogene. We showed that ITPKA expression is up-regulated in many forms of cancers, including lung and breast cancers, and that overexpressed ITPKA contributes to tumorigenesis. We also demonstrated that ITPKA expression is regulated by epigenetic DNA methylation of ITPKA gene body through modulation of the binding of SP1 transcription factor to the ITPKA promoter. ITPKA gene body displayed low or absent levels of methylation in most normal tissue but was significantly methylated in malignant tumors. In lung cancer, ITPKA gene body methylation first appeared at the in situ carcinoma stage and progressively increased after invasion. Conclusions: ITPKA is a potential oncogene that it is overexpressed in most tumors, and its overexpression promotes tumorigenesis. ITPKA gene body methylation regulates its expression and thus serves as a novel and potential biomarker for early cancer detection.

AB - Introduction: Despite recent advances in cancer therapy, the overall 5-year survival rate of patients with lung cancer remains low. The aim of our study was to search for novel markers for early diagnosis in patients with lung cancer. Methods: Complementary DNA microarray analysis was performed in primary lung adenocarcinomas and cell lines to search for differentially expressed genes, followed by in vivo and in vitro tumorigenic assays to characterize the oncogenic potential of the candidate genes. Gene body methylation was analyzed by 450K methylation array, bisulfite sequencing, and quantitative methylation-specific polymerase chain reaction assays. In silico analysis of The Cancer Genome Atlas data set was also performed. Results: Inositol-Trisphosphate 3-kinase A gene (ITPKA), a kinase with limited tissue distribution, was identified as a potential oncogene. We showed that ITPKA expression is up-regulated in many forms of cancers, including lung and breast cancers, and that overexpressed ITPKA contributes to tumorigenesis. We also demonstrated that ITPKA expression is regulated by epigenetic DNA methylation of ITPKA gene body through modulation of the binding of SP1 transcription factor to the ITPKA promoter. ITPKA gene body displayed low or absent levels of methylation in most normal tissue but was significantly methylated in malignant tumors. In lung cancer, ITPKA gene body methylation first appeared at the in situ carcinoma stage and progressively increased after invasion. Conclusions: ITPKA is a potential oncogene that it is overexpressed in most tumors, and its overexpression promotes tumorigenesis. ITPKA gene body methylation regulates its expression and thus serves as a novel and potential biomarker for early cancer detection.

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