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

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 -