Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis

Emma H Allott; Melissa J Morine; Joanne Lysaght; Sarah A McGarrigle; Claire L Donohoe; John V Reynolds; Helen M Roche; Graham P Pidgeon

doi:10.1038/ctg.2012.5

Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis

Emma H Allott, Melissa J Morine, Joanne Lysaght, Sarah A McGarrigle, Claire L Donohoe, John V Reynolds, Helen M Roche, Graham P Pidgeon

Research output: Contribution to journal › Article › peer-review

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Abstract

OBJECTIVES: Obesity is linked to increased mortality from many cancer types, and esophageal adenocarcinoma (EAC) displays one of the strongest epidemiological associations. The aims of this study are to dissect molecular pathways linking obesity with EAC and to determine if obesity is linked to increased aggressiveness of this disease.

METHODS: Affymetrix microarrays identified altered signaling pathways in an EAC cell line following coculture with visceral adipose tissue or isolated adipocytes from viscerally obese EAC patients (n=6). Differentially expressed genes were subsequently investigated in patient tumor biopsies by quantitative reverse transcriptase PCR and examined with respect to obesity status, tumor biology, and patient survival.

RESULTS: Visceral adipose tissue induced expression of genes involved in epithelial mesenchymal transition (EMT), plasminogen activator inhibitor (PAI)-1, and transcription factor SNAI2, in an EAC cell line. In EAC patient tumor biopsies from obese patients, we noted elevated expression of these genes, together with reduced expression of epithelial marker E-cadherin. SNAI2 was associated with EAC prognosis.

CONCLUSIONS: Expression of EMT genes, PAI-1 and SNAI2, was elevated in tumors of obese EAC patients, and SNAI2 was associated with poor survival. Genes deregulated in obesity and associated with prognosis may represent potential targets for treatment stratification of obese EAC patients.

Original language	English
Pages (from-to)	e12
Journal	Clinical and translational gastroenterology
Volume	3
DOIs	https://doi.org/10.1038/ctg.2012.5
Publication status	Published - 19 Apr 2012
Externally published	Yes

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@article{c293fef39e954819b40d4db45928b4d5,

title = "Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis",

abstract = "OBJECTIVES: Obesity is linked to increased mortality from many cancer types, and esophageal adenocarcinoma (EAC) displays one of the strongest epidemiological associations. The aims of this study are to dissect molecular pathways linking obesity with EAC and to determine if obesity is linked to increased aggressiveness of this disease.METHODS: Affymetrix microarrays identified altered signaling pathways in an EAC cell line following coculture with visceral adipose tissue or isolated adipocytes from viscerally obese EAC patients (n=6). Differentially expressed genes were subsequently investigated in patient tumor biopsies by quantitative reverse transcriptase PCR and examined with respect to obesity status, tumor biology, and patient survival.RESULTS: Visceral adipose tissue induced expression of genes involved in epithelial mesenchymal transition (EMT), plasminogen activator inhibitor (PAI)-1, and transcription factor SNAI2, in an EAC cell line. In EAC patient tumor biopsies from obese patients, we noted elevated expression of these genes, together with reduced expression of epithelial marker E-cadherin. SNAI2 was associated with EAC prognosis.CONCLUSIONS: Expression of EMT genes, PAI-1 and SNAI2, was elevated in tumors of obese EAC patients, and SNAI2 was associated with poor survival. Genes deregulated in obesity and associated with prognosis may represent potential targets for treatment stratification of obese EAC patients.",

author = "Allott, {Emma H} and Morine, {Melissa J} and Joanne Lysaght and McGarrigle, {Sarah A} and Donohoe, {Claire L} and Reynolds, {John V} and Roche, {Helen M} and Pidgeon, {Graham P}",

year = "2012",

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doi = "10.1038/ctg.2012.5",

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volume = "3",

pages = "e12",

journal = "Clinical and translational gastroenterology",

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T1 - Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis

AU - Allott, Emma H

AU - Morine, Melissa J

AU - Lysaght, Joanne

AU - McGarrigle, Sarah A

AU - Donohoe, Claire L

AU - Reynolds, John V

AU - Roche, Helen M

AU - Pidgeon, Graham P

PY - 2012/4/19

Y1 - 2012/4/19

N2 - OBJECTIVES: Obesity is linked to increased mortality from many cancer types, and esophageal adenocarcinoma (EAC) displays one of the strongest epidemiological associations. The aims of this study are to dissect molecular pathways linking obesity with EAC and to determine if obesity is linked to increased aggressiveness of this disease.METHODS: Affymetrix microarrays identified altered signaling pathways in an EAC cell line following coculture with visceral adipose tissue or isolated adipocytes from viscerally obese EAC patients (n=6). Differentially expressed genes were subsequently investigated in patient tumor biopsies by quantitative reverse transcriptase PCR and examined with respect to obesity status, tumor biology, and patient survival.RESULTS: Visceral adipose tissue induced expression of genes involved in epithelial mesenchymal transition (EMT), plasminogen activator inhibitor (PAI)-1, and transcription factor SNAI2, in an EAC cell line. In EAC patient tumor biopsies from obese patients, we noted elevated expression of these genes, together with reduced expression of epithelial marker E-cadherin. SNAI2 was associated with EAC prognosis.CONCLUSIONS: Expression of EMT genes, PAI-1 and SNAI2, was elevated in tumors of obese EAC patients, and SNAI2 was associated with poor survival. Genes deregulated in obesity and associated with prognosis may represent potential targets for treatment stratification of obese EAC patients.

AB - OBJECTIVES: Obesity is linked to increased mortality from many cancer types, and esophageal adenocarcinoma (EAC) displays one of the strongest epidemiological associations. The aims of this study are to dissect molecular pathways linking obesity with EAC and to determine if obesity is linked to increased aggressiveness of this disease.METHODS: Affymetrix microarrays identified altered signaling pathways in an EAC cell line following coculture with visceral adipose tissue or isolated adipocytes from viscerally obese EAC patients (n=6). Differentially expressed genes were subsequently investigated in patient tumor biopsies by quantitative reverse transcriptase PCR and examined with respect to obesity status, tumor biology, and patient survival.RESULTS: Visceral adipose tissue induced expression of genes involved in epithelial mesenchymal transition (EMT), plasminogen activator inhibitor (PAI)-1, and transcription factor SNAI2, in an EAC cell line. In EAC patient tumor biopsies from obese patients, we noted elevated expression of these genes, together with reduced expression of epithelial marker E-cadherin. SNAI2 was associated with EAC prognosis.CONCLUSIONS: Expression of EMT genes, PAI-1 and SNAI2, was elevated in tumors of obese EAC patients, and SNAI2 was associated with poor survival. Genes deregulated in obesity and associated with prognosis may represent potential targets for treatment stratification of obese EAC patients.

U2 - 10.1038/ctg.2012.5

DO - 10.1038/ctg.2012.5

M3 - Article

C2 - 23238211

SN - 2155-384X

VL - 3

SP - e12

JO - Clinical and translational gastroenterology

JF - Clinical and translational gastroenterology

ER -

Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis

Abstract

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