Possible predisposition for colorectal carcinogenesis due to altered gene expressions in normal appearing mucosa from patients with colorectal neoplasia.
Biomarkers, Tumor
/ genetics
Colon
/ pathology
Colorectal Neoplasms
/ genetics
Cyclooxygenase 1
/ metabolism
Dinoprostone
/ metabolism
Extracellular Signal-Regulated MAP Kinases
/ genetics
Female
Genetic Predisposition to Disease
/ genetics
Group IV Phospholipases A2
/ genetics
Humans
Hydroxyprostaglandin Dehydrogenases
/ metabolism
Intestinal Mucosa
/ metabolism
Male
Middle Aged
Protein Phosphatase 2
/ genetics
Proto-Oncogene Proteins c-akt
/ genetics
RNA, Messenger
/ metabolism
Receptors, Prostaglandin E, EP3 Subtype
/ genetics
Signal Transduction
/ genetics
Up-Regulation
beta Catenin
/ metabolism
Akt
Colorectal cancer
Extracellular signal-regulated kinase (ERK)
Prostaglandin E2
β-Catenin
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
28 Jun 2019
28 Jun 2019
Historique:
received:
19
06
2018
accepted:
13
06
2019
entrez:
30
6
2019
pubmed:
30
6
2019
medline:
27
11
2019
Statut:
epublish
Résumé
Investigations 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. Biopsies 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/β-catenin pathways as well as for selected phosphatases and several entities associated with prostaglandin E2 (PGE We 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. Present 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.
Sections du résumé
BACKGROUND
BACKGROUND
Investigations 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.
METHODS
METHODS
Biopsies 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/β-catenin pathways as well as for selected phosphatases and several entities associated with prostaglandin E2 (PGE
RESULTS
RESULTS
We 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.
CONCLUSION
CONCLUSIONS
Present 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.
Identifiants
pubmed: 31253108
doi: 10.1186/s12885-019-5833-8
pii: 10.1186/s12885-019-5833-8
pmc: PMC6599319
doi:
Substances chimiques
Biomarkers, Tumor
0
CTNNB1 protein, human
0
PPP2R1B protein, human
0
PTGER3 protein, human
0
RNA, Messenger
0
Receptors, Prostaglandin E, EP3 Subtype
0
beta Catenin
0
Hydroxyprostaglandin Dehydrogenases
EC 1.1.1.-
15-hydroxyprostaglandin dehydrogenase
EC 1.1.1.141
Cyclooxygenase 1
EC 1.14.99.1
PTGS1 protein, human
EC 1.14.99.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Group IV Phospholipases A2
EC 3.1.1.4
PLA2G4A protein, human
EC 3.1.1.4
Protein Phosphatase 2
EC 3.1.3.16
Dinoprostone
K7Q1JQR04M
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
643Subventions
Organisme : The Danish Cancer Society
ID : R141-A8964-15-S7
Organisme : Else and Mogens Wedell-Wedellborgs Foundation
ID : 30-17-1
Organisme : Civilingeniør Bent Bøgh og Hustru Inge Bøghs Fond
ID : Award number not provided by funder
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