Metabolic profiling detects field effects in nondysplastic tissue from esophageal cancer patients

Danny Yakoub, Hector C. Keun, Robert Goldin, George B. Hanna

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The variable rate of missed cancer in endoscopic biopsies and lack of other biomarkers reduce the effectiveness of surveillance programs in esophageal cancer. Based on the "field cancerization" hypothesis that tumors arise within a transformed field with an altered biochemical phenotype, we sought to test if metabolic profiling could differentiate between histologically normal tissue from individuals with and without esophageal cancer. Thirty-five patients with esophageal adenocarcinoma and 52 age-matched controls participated in the study. Using 1H magic angle spinning-nuclear magnetic resonance spectroscopy of intact tissue, we generated metabolic profiles of tumor tissue, proximal histologically normal mucosa from cancer patients (PHINOM), and proximal histologically normal mucosa from a control group. Using multivariate regression and receiver-operator characteristic analysis, we identified a panel of metabolites discriminating malignant and histologically normal tissues from cancer patients and from that of controls. Whereas 26% and 12% of the spectral profile regions were uniquely discriminating tumor or control tissue, respectively, 5% of the profile exhibited a significant progressive change in signal intensity from controls to PHINOM to tumor. Regions identified were assigned to phosphocholine (PC), glutamate (Glu), myo-inositol, adenosine-containing compounds, uridine-containing compounds, and inosine. In particular, the PC/Glu ratio in histologically normal tissue signified the presence of esophageal cancer (n = 123; area under the curve, 0.84; P < 0.001). In conclusion, our findings support the hypothesis of the presence of metabonomic field effects in esophageal cancer, even in non-Barrett's segments. This indicates that metabolic profiling of tissue can potentially play a role in the surveillance of cancer by reporting on the phenotypic consequences of field cancerization.

Original languageEnglish (US)
Pages (from-to)9129-9136
Number of pages8
JournalCancer Research
Volume70
Issue number22
DOIs
StatePublished - Nov 15 2010

Fingerprint

Esophageal Neoplasms
Neoplasms
Mucous Membrane
Phosphorylcholine
Glutamic Acid
Inosine
Metabolomics
Metabolome
Uridine
Program Evaluation
Inositol
Adenosine
Area Under Curve
Adenocarcinoma
Magnetic Resonance Spectroscopy
Biomarkers
Phenotype
Biopsy
Control Groups

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Metabolic profiling detects field effects in nondysplastic tissue from esophageal cancer patients. / Yakoub, Danny; Keun, Hector C.; Goldin, Robert; Hanna, George B.

In: Cancer Research, Vol. 70, No. 22, 15.11.2010, p. 9129-9136.

Research output: Contribution to journalArticle

Yakoub, Danny ; Keun, Hector C. ; Goldin, Robert ; Hanna, George B. / Metabolic profiling detects field effects in nondysplastic tissue from esophageal cancer patients. In: Cancer Research. 2010 ; Vol. 70, No. 22. pp. 9129-9136.
@article{428b236be27c4d5daf0e576742292f4f,
title = "Metabolic profiling detects field effects in nondysplastic tissue from esophageal cancer patients",
abstract = "The variable rate of missed cancer in endoscopic biopsies and lack of other biomarkers reduce the effectiveness of surveillance programs in esophageal cancer. Based on the {"}field cancerization{"} hypothesis that tumors arise within a transformed field with an altered biochemical phenotype, we sought to test if metabolic profiling could differentiate between histologically normal tissue from individuals with and without esophageal cancer. Thirty-five patients with esophageal adenocarcinoma and 52 age-matched controls participated in the study. Using 1H magic angle spinning-nuclear magnetic resonance spectroscopy of intact tissue, we generated metabolic profiles of tumor tissue, proximal histologically normal mucosa from cancer patients (PHINOM), and proximal histologically normal mucosa from a control group. Using multivariate regression and receiver-operator characteristic analysis, we identified a panel of metabolites discriminating malignant and histologically normal tissues from cancer patients and from that of controls. Whereas 26{\%} and 12{\%} of the spectral profile regions were uniquely discriminating tumor or control tissue, respectively, 5{\%} of the profile exhibited a significant progressive change in signal intensity from controls to PHINOM to tumor. Regions identified were assigned to phosphocholine (PC), glutamate (Glu), myo-inositol, adenosine-containing compounds, uridine-containing compounds, and inosine. In particular, the PC/Glu ratio in histologically normal tissue signified the presence of esophageal cancer (n = 123; area under the curve, 0.84; P < 0.001). In conclusion, our findings support the hypothesis of the presence of metabonomic field effects in esophageal cancer, even in non-Barrett's segments. This indicates that metabolic profiling of tissue can potentially play a role in the surveillance of cancer by reporting on the phenotypic consequences of field cancerization.",
author = "Danny Yakoub and Keun, {Hector C.} and Robert Goldin and Hanna, {George B.}",
year = "2010",
month = "11",
day = "15",
doi = "10.1158/0008-5472.CAN-10-1566",
language = "English (US)",
volume = "70",
pages = "9129--9136",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "22",

}

TY - JOUR

T1 - Metabolic profiling detects field effects in nondysplastic tissue from esophageal cancer patients

AU - Yakoub, Danny

AU - Keun, Hector C.

AU - Goldin, Robert

AU - Hanna, George B.

PY - 2010/11/15

Y1 - 2010/11/15

N2 - The variable rate of missed cancer in endoscopic biopsies and lack of other biomarkers reduce the effectiveness of surveillance programs in esophageal cancer. Based on the "field cancerization" hypothesis that tumors arise within a transformed field with an altered biochemical phenotype, we sought to test if metabolic profiling could differentiate between histologically normal tissue from individuals with and without esophageal cancer. Thirty-five patients with esophageal adenocarcinoma and 52 age-matched controls participated in the study. Using 1H magic angle spinning-nuclear magnetic resonance spectroscopy of intact tissue, we generated metabolic profiles of tumor tissue, proximal histologically normal mucosa from cancer patients (PHINOM), and proximal histologically normal mucosa from a control group. Using multivariate regression and receiver-operator characteristic analysis, we identified a panel of metabolites discriminating malignant and histologically normal tissues from cancer patients and from that of controls. Whereas 26% and 12% of the spectral profile regions were uniquely discriminating tumor or control tissue, respectively, 5% of the profile exhibited a significant progressive change in signal intensity from controls to PHINOM to tumor. Regions identified were assigned to phosphocholine (PC), glutamate (Glu), myo-inositol, adenosine-containing compounds, uridine-containing compounds, and inosine. In particular, the PC/Glu ratio in histologically normal tissue signified the presence of esophageal cancer (n = 123; area under the curve, 0.84; P < 0.001). In conclusion, our findings support the hypothesis of the presence of metabonomic field effects in esophageal cancer, even in non-Barrett's segments. This indicates that metabolic profiling of tissue can potentially play a role in the surveillance of cancer by reporting on the phenotypic consequences of field cancerization.

AB - The variable rate of missed cancer in endoscopic biopsies and lack of other biomarkers reduce the effectiveness of surveillance programs in esophageal cancer. Based on the "field cancerization" hypothesis that tumors arise within a transformed field with an altered biochemical phenotype, we sought to test if metabolic profiling could differentiate between histologically normal tissue from individuals with and without esophageal cancer. Thirty-five patients with esophageal adenocarcinoma and 52 age-matched controls participated in the study. Using 1H magic angle spinning-nuclear magnetic resonance spectroscopy of intact tissue, we generated metabolic profiles of tumor tissue, proximal histologically normal mucosa from cancer patients (PHINOM), and proximal histologically normal mucosa from a control group. Using multivariate regression and receiver-operator characteristic analysis, we identified a panel of metabolites discriminating malignant and histologically normal tissues from cancer patients and from that of controls. Whereas 26% and 12% of the spectral profile regions were uniquely discriminating tumor or control tissue, respectively, 5% of the profile exhibited a significant progressive change in signal intensity from controls to PHINOM to tumor. Regions identified were assigned to phosphocholine (PC), glutamate (Glu), myo-inositol, adenosine-containing compounds, uridine-containing compounds, and inosine. In particular, the PC/Glu ratio in histologically normal tissue signified the presence of esophageal cancer (n = 123; area under the curve, 0.84; P < 0.001). In conclusion, our findings support the hypothesis of the presence of metabonomic field effects in esophageal cancer, even in non-Barrett's segments. This indicates that metabolic profiling of tissue can potentially play a role in the surveillance of cancer by reporting on the phenotypic consequences of field cancerization.

UR - http://www.scopus.com/inward/record.url?scp=78549258540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78549258540&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-10-1566

DO - 10.1158/0008-5472.CAN-10-1566

M3 - Article

VL - 70

SP - 9129

EP - 9136

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 22

ER -