Possible predisposition for colorectal carcinogenesis due to altered gene expressions in normal appearing mucosa from patients with colorectal neoplasia

Christian Hunnicke Petersen; Badar Mahmood; Christoffer Badsted; Tina Dahlby; Hanne Borger Rasmussen; Mark Berner Hansen; Niels Bindslev

doi:10.1186/s12885-019-5833-8

Possible predisposition for colorectal carcinogenesis due to altered gene expressions in normal appearing mucosa from patients with colorectal neoplasia

Christian Hunnicke Petersen, Badar Mahmood, Christoffer Badsted, Tina Dahlby, Hanne Borger Rasmussen, Mark Berner Hansen, Niels Bindslev

17 Downloads (Pure)

Abstract

BackgroundInvestigations of colorectal carcinogenesis have mainly focused on examining neoplastic tissue. With our aim of identifying potentially cancer-predisposing molecular compositions, we chose a different approach by examining endoscopically normal appearing colonic mucosa of patients with and without colorectal neoplasia (CRN). Directed by this focus, we selected 18 genes that were previously found with altered expression in colorectal cancer affected mucosa.MethodsBiopsies of colonic mucosa were sampled from 27 patients referred for colonoscopy on suspicion of colorectal disease. Of these, 14 patients had present or previous CRN and the remaining 13 patients served as controls. Using qPCR and Western blot technique, we investigated mRNA and protein expressions. Expressions were investigated for selected kinases in the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK), the phosphoinositide 3-kinase/Akt, and the Wnt/-catenin pathways as well as for selected phosphatases and several entities associated with prostaglandin E2 (PGE(2)) signaling. Colonic mucosal contents of PGE(2) and PGE(2) metabolites were determined by use of ELISA.ResultsWe found up-regulation of ERK1, ERK2, Akt1, Akt2, PLA2G4A, prostanoid receptor EP3 and phosphatase scaffold subunit PPP2R1B mRNA expression in normal appearing colonic mucosa of CRN patients compared to controls.ConclusionPresent study supports that even normal appearing mucosa of CRN patients differs from that of non-CRN patients at a molecular level. Especially expression of ERK1 mRNA was increased (p=0.007) in CRN group. ERK1 may therefore be considered a potential candidate gene as predictive biomarker for developing CRN. Further validation in larger cohorts are required to determine such predictive use in translational medicine and clinics.

Original language	English
Article number	643
Journal	BMC Cancer
Volume	19
Number of pages	13
ISSN	1471-2407
DOIs	https://doi.org/10.1186/s12885-019-5833-8
Publication status	Published - 28 Jun 2019

Keywords

Extracellular signal-regulated kinase (ERK)
Akt
Prostaglandin E2
-Catenin
Colorectal cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/s12885-019-5833-8

BMCoa-articleFinal published version, 5.28 MBLicence: CC BY

Cite this

@article{dd3de16041f24b75b54e6b1025c31d01,

title = "Possible predisposition for colorectal carcinogenesis due to altered gene expressions in normal appearing mucosa from patients with colorectal neoplasia",

abstract = "BackgroundInvestigations of colorectal carcinogenesis have mainly focused on examining neoplastic tissue. With our aim of identifying potentially cancer-predisposing molecular compositions, we chose a different approach by examining endoscopically normal appearing colonic mucosa of patients with and without colorectal neoplasia (CRN). Directed by this focus, we selected 18 genes that were previously found with altered expression in colorectal cancer affected mucosa.MethodsBiopsies of colonic mucosa were sampled from 27 patients referred for colonoscopy on suspicion of colorectal disease. Of these, 14 patients had present or previous CRN and the remaining 13 patients served as controls. Using qPCR and Western blot technique, we investigated mRNA and protein expressions. Expressions were investigated for selected kinases in the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK), the phosphoinositide 3-kinase/Akt, and the Wnt/-catenin pathways as well as for selected phosphatases and several entities associated with prostaglandin E2 (PGE(2)) signaling. Colonic mucosal contents of PGE(2) and PGE(2) metabolites were determined by use of ELISA.ResultsWe found up-regulation of ERK1, ERK2, Akt1, Akt2, PLA2G4A, prostanoid receptor EP3 and phosphatase scaffold subunit PPP2R1B mRNA expression in normal appearing colonic mucosa of CRN patients compared to controls.ConclusionPresent study supports that even normal appearing mucosa of CRN patients differs from that of non-CRN patients at a molecular level. Especially expression of ERK1 mRNA was increased (p=0.007) in CRN group. ERK1 may therefore be considered a potential candidate gene as predictive biomarker for developing CRN. Further validation in larger cohorts are required to determine such predictive use in translational medicine and clinics.",

keywords = "Extracellular signal-regulated kinase (ERK), Akt, Prostaglandin E2, -Catenin, Colorectal cancer",

author = "Petersen, {Christian Hunnicke} and Badar Mahmood and Christoffer Badsted and Tina Dahlby and Rasmussen, {Hanne Borger} and Hansen, {Mark Berner} and Niels Bindslev",

year = "2019",

month = jun,

day = "28",

doi = "10.1186/s12885-019-5833-8",

language = "English",

volume = "19",

journal = "BMC Cancer",

issn = "1471-2407",

publisher = "BioMed Central Ltd.",

}

TY - JOUR

T1 - Possible predisposition for colorectal carcinogenesis due to altered gene expressions in normal appearing mucosa from patients with colorectal neoplasia

AU - Petersen, Christian Hunnicke

AU - Mahmood, Badar

AU - Badsted, Christoffer

AU - Dahlby, Tina

AU - Rasmussen, Hanne Borger

AU - Hansen, Mark Berner

AU - Bindslev, Niels

PY - 2019/6/28

Y1 - 2019/6/28

N2 - BackgroundInvestigations of colorectal carcinogenesis have mainly focused on examining neoplastic tissue. With our aim of identifying potentially cancer-predisposing molecular compositions, we chose a different approach by examining endoscopically normal appearing colonic mucosa of patients with and without colorectal neoplasia (CRN). Directed by this focus, we selected 18 genes that were previously found with altered expression in colorectal cancer affected mucosa.MethodsBiopsies of colonic mucosa were sampled from 27 patients referred for colonoscopy on suspicion of colorectal disease. Of these, 14 patients had present or previous CRN and the remaining 13 patients served as controls. Using qPCR and Western blot technique, we investigated mRNA and protein expressions. Expressions were investigated for selected kinases in the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK), the phosphoinositide 3-kinase/Akt, and the Wnt/-catenin pathways as well as for selected phosphatases and several entities associated with prostaglandin E2 (PGE(2)) signaling. Colonic mucosal contents of PGE(2) and PGE(2) metabolites were determined by use of ELISA.ResultsWe found up-regulation of ERK1, ERK2, Akt1, Akt2, PLA2G4A, prostanoid receptor EP3 and phosphatase scaffold subunit PPP2R1B mRNA expression in normal appearing colonic mucosa of CRN patients compared to controls.ConclusionPresent study supports that even normal appearing mucosa of CRN patients differs from that of non-CRN patients at a molecular level. Especially expression of ERK1 mRNA was increased (p=0.007) in CRN group. ERK1 may therefore be considered a potential candidate gene as predictive biomarker for developing CRN. Further validation in larger cohorts are required to determine such predictive use in translational medicine and clinics.

AB - BackgroundInvestigations of colorectal carcinogenesis have mainly focused on examining neoplastic tissue. With our aim of identifying potentially cancer-predisposing molecular compositions, we chose a different approach by examining endoscopically normal appearing colonic mucosa of patients with and without colorectal neoplasia (CRN). Directed by this focus, we selected 18 genes that were previously found with altered expression in colorectal cancer affected mucosa.MethodsBiopsies of colonic mucosa were sampled from 27 patients referred for colonoscopy on suspicion of colorectal disease. Of these, 14 patients had present or previous CRN and the remaining 13 patients served as controls. Using qPCR and Western blot technique, we investigated mRNA and protein expressions. Expressions were investigated for selected kinases in the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK), the phosphoinositide 3-kinase/Akt, and the Wnt/-catenin pathways as well as for selected phosphatases and several entities associated with prostaglandin E2 (PGE(2)) signaling. Colonic mucosal contents of PGE(2) and PGE(2) metabolites were determined by use of ELISA.ResultsWe found up-regulation of ERK1, ERK2, Akt1, Akt2, PLA2G4A, prostanoid receptor EP3 and phosphatase scaffold subunit PPP2R1B mRNA expression in normal appearing colonic mucosa of CRN patients compared to controls.ConclusionPresent study supports that even normal appearing mucosa of CRN patients differs from that of non-CRN patients at a molecular level. Especially expression of ERK1 mRNA was increased (p=0.007) in CRN group. ERK1 may therefore be considered a potential candidate gene as predictive biomarker for developing CRN. Further validation in larger cohorts are required to determine such predictive use in translational medicine and clinics.

KW - Extracellular signal-regulated kinase (ERK)

KW - Akt

KW - Prostaglandin E2

KW - -Catenin

KW - Colorectal cancer

U2 - 10.1186/s12885-019-5833-8

DO - 10.1186/s12885-019-5833-8

M3 - Journal article

C2 - 31253108

SN - 1471-2407

VL - 19

JO - BMC Cancer

JF - BMC Cancer

M1 - 643

ER -

Possible predisposition for colorectal carcinogenesis due to altered gene expressions in normal appearing mucosa from patients with colorectal neoplasia

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this