Metabolomic dynamic analysis of hypoxia in MDA-MB-231 and the comparison with inferred metabolites from transcriptomics data

I. Lin Tsai, Tien Chueh Kuo, Tsung Jung Ho, Yeu Chern Harn, San Yuan Wang, Wen Mei Fu, Ching Hua Kuo, Yufeng Jane Tseng

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis.

Original languageEnglish
Pages (from-to)491-510
Number of pages20
JournalCancers
Volume5
Issue number2
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

Fingerprint

Metabolomics
Gene Expression
Cell Line
Tumor Microenvironment
Gluconeogenesis
Metabolome
Glycolysis
Metabolic Networks and Pathways
Pyruvic Acid
Proline
Arginine
Magnetic Resonance Spectroscopy
Multivariate Analysis
Breast Neoplasms
Neoplasm Metastasis
Phenotype
Hypoxia
Tumor Hypoxia
Therapeutics

Keywords

  • H-NMR spectroscopy
  • Metabolic network
  • Metabolomics
  • Multivariate analysis
  • Tumor hypoxia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Metabolomic dynamic analysis of hypoxia in MDA-MB-231 and the comparison with inferred metabolites from transcriptomics data. / Tsai, I. Lin; Kuo, Tien Chueh; Ho, Tsung Jung; Harn, Yeu Chern; Wang, San Yuan; Fu, Wen Mei; Kuo, Ching Hua; Tseng, Yufeng Jane.

In: Cancers, Vol. 5, No. 2, 06.2013, p. 491-510.

Research output: Contribution to journalArticle

Tsai, I. Lin ; Kuo, Tien Chueh ; Ho, Tsung Jung ; Harn, Yeu Chern ; Wang, San Yuan ; Fu, Wen Mei ; Kuo, Ching Hua ; Tseng, Yufeng Jane. / Metabolomic dynamic analysis of hypoxia in MDA-MB-231 and the comparison with inferred metabolites from transcriptomics data. In: Cancers. 2013 ; Vol. 5, No. 2. pp. 491-510.
@article{da5a68a8be194cf7b65fa6fa6e5724c3,
title = "Metabolomic dynamic analysis of hypoxia in MDA-MB-231 and the comparison with inferred metabolites from transcriptomics data",
abstract = "Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis.",
keywords = "H-NMR spectroscopy, Metabolic network, Metabolomics, Multivariate analysis, Tumor hypoxia",
author = "Tsai, {I. Lin} and Kuo, {Tien Chueh} and Ho, {Tsung Jung} and Harn, {Yeu Chern} and Wang, {San Yuan} and Fu, {Wen Mei} and Kuo, {Ching Hua} and Tseng, {Yufeng Jane}",
year = "2013",
month = "6",
doi = "10.3390/cancers5020491",
language = "English",
volume = "5",
pages = "491--510",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "2",

}

TY - JOUR

T1 - Metabolomic dynamic analysis of hypoxia in MDA-MB-231 and the comparison with inferred metabolites from transcriptomics data

AU - Tsai, I. Lin

AU - Kuo, Tien Chueh

AU - Ho, Tsung Jung

AU - Harn, Yeu Chern

AU - Wang, San Yuan

AU - Fu, Wen Mei

AU - Kuo, Ching Hua

AU - Tseng, Yufeng Jane

PY - 2013/6

Y1 - 2013/6

N2 - Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis.

AB - Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis.

KW - H-NMR spectroscopy

KW - Metabolic network

KW - Metabolomics

KW - Multivariate analysis

KW - Tumor hypoxia

UR - http://www.scopus.com/inward/record.url?scp=84878175490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878175490&partnerID=8YFLogxK

U2 - 10.3390/cancers5020491

DO - 10.3390/cancers5020491

M3 - Article

C2 - 24216987

AN - SCOPUS:84878175490

VL - 5

SP - 491

EP - 510

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 2

ER -