Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ analysis
Biopsy
Cohort Studies
Colon
/ diagnostic imaging
Colonoscopy
Colorectal Neoplasms
/ diagnostic imaging
Cyclooxygenase 2
/ analysis
Dinoprostone
/ analysis
Female
Gene Expression Regulation, Neoplastic
HT29 Cells
Humans
Intestinal Mucosa
/ diagnostic imaging
Male
Metabolome
Metabolomics
/ methods
Middle Aged
Protein Processing, Post-Translational
Proteome
/ analysis
Proteomics
/ methods
Spain
Carcinoma
Colon
Cyclooxygenase
High resolution magic angle spinning
Prostaglandin
Proteomics
Journal
World journal of gastroenterology
ISSN: 2219-2840
Titre abrégé: World J Gastroenterol
Pays: United States
ID NLM: 100883448
Informations de publication
Date de publication:
28 Jan 2019
28 Jan 2019
Historique:
received:
17
10
2018
revised:
21
12
2018
accepted:
09
01
2019
entrez:
1
2
2019
pubmed:
1
2
2019
medline:
6
4
2019
Statut:
ppublish
Résumé
Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2 (COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans. To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile. Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge (Barcelona, Spain) and Germans Trias i Pujol University Hospital (Campus Can Ruti) (Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F (PNGase F). Prostaglandin E Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients In our colorectal cancer cohort, tumor tissue presents a differential COX-2 expression pattern with lower enzymatic activity that can be related to an altered metabolic and proteomic profile.
Sections du résumé
BACKGROUND
BACKGROUND
Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2 (COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.
AIM
OBJECTIVE
To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.
METHODS
METHODS
Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge (Barcelona, Spain) and Germans Trias i Pujol University Hospital (Campus Can Ruti) (Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F (PNGase F). Prostaglandin E
RESULTS
RESULTS
Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients
CONCLUSION
CONCLUSIONS
In our colorectal cancer cohort, tumor tissue presents a differential COX-2 expression pattern with lower enzymatic activity that can be related to an altered metabolic and proteomic profile.
Identifiants
pubmed: 30700940
doi: 10.3748/wjg.v25.i4.433
pmc: PMC6350170
doi:
Substances chimiques
Biomarkers, Tumor
0
Proteome
0
Cyclooxygenase 2
EC 1.14.99.1
PTGS2 protein, human
EC 1.14.99.1
Dinoprostone
K7Q1JQR04M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
433-446Déclaration de conflit d'intérêts
Conflict-of-interest statement: MAP is cofounder and equity holder of Aniling, a biotech company with no interests in this work. MAP lab has received research funding from Celgene. The rest of the authors declare no conflict of interest.
Références
Carcinogenesis. 2000 Jan;21(1):69-77
pubmed: 10607736
J Pathol. 2002 Dec;198(4):428-34
pubmed: 12434411
Curr Pharm Des. 2003;9(27):2229-51
pubmed: 14529404
Cancer Metastasis Rev. 2004 Jan-Jun;23(1-2):63-75
pubmed: 15000150
J Biol Chem. 2005 Feb 4;280(5):3217-23
pubmed: 15542609
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):12098-102
pubmed: 16880406
FEBS Lett. 2006 Dec 11;580(28-29):6533-6
pubmed: 17113084
Mol Cell Proteomics. 2008 Jun;7(6):1135-45
pubmed: 18303013
Carcinogenesis. 2009 Mar;30(3):377-86
pubmed: 19136477
J Immunol. 2009 Mar 15;182(6):3819-26
pubmed: 19265161
Dis Colon Rectum. 2009 Mar;52(3):520-5
pubmed: 19333056
Curr Genomics. 2008 Dec;9(8):556-70
pubmed: 19516963
J Proteome Res. 2009 Apr;8(4):1792-6
pubmed: 19714873
Br J Cancer. 2010 Jan 5;102(1):1-7
pubmed: 19935796
Oncogene. 2010 Feb 11;29(6):781-8
pubmed: 19946329
Cancer Chemother Pharmacol. 2011 Jul;68(1):29-36
pubmed: 20821329
Integr Biol (Camb). 2011 Apr;3(4):279-96
pubmed: 21340093
J Proteome Res. 2011 Jul 1;10(7):3040-9
pubmed: 21526778
Cancer Res. 2011 Nov 15;71(22):6921-5
pubmed: 22084445
PLoS One. 2011;6(11):e27718
pubmed: 22125622
Pharmacol Res. 2012 Apr;65(4):445-50
pubmed: 22245433
Breast Cancer Res. 2012 Apr 19;14(2):207
pubmed: 22515594
Asian Pac J Cancer Prev. 2012;13(4):1663-6
pubmed: 22799385
PLoS One. 2013;8(3):e58891
pubmed: 23527044
Ann Surg. 2014 Jun;259(6):1138-49
pubmed: 23860197
BMC Cancer. 2013 Oct 30;13:511
pubmed: 24171795
Mol Cell Proteomics. 2014 May;13(5):1198-218
pubmed: 24567419
World J Gastroenterol. 2014 Apr 14;20(14):3804-24
pubmed: 24744574
J Natl Cancer Inst. 2014 Dec 01;107(1):358
pubmed: 25465874
J Proteomics. 2015 Aug 3;126:54-67
pubmed: 26054784
Gastroenterology. 2015 Dec;149(7):1884-1895.e4
pubmed: 26261008
J Transl Med. 2015 Sep 23;13:313
pubmed: 26394751
Cancer Cell Int. 2015 Nov 05;15:106
pubmed: 26549987
Int J Clin Exp Med. 2015 Sep 15;8(9):16071-6
pubmed: 26629114
Sci Rep. 2016 Feb 15;6:20790
pubmed: 26876567
Pharmacol Ther. 2016 Aug;164:135-43
pubmed: 27113410
Nat Rev Dis Primers. 2015 Nov 05;1:15065
pubmed: 27189416
Nat Med. 2016 Sep 7;22(9):976-86
pubmed: 27603132
Stem Cells Int. 2016;2016:2048731
pubmed: 27882058
Carcinogenesis. 2017 Feb 1;38(2):119-133
pubmed: 27993896
Sci Rep. 2017 Feb 09;7:42436
pubmed: 28181595
Cell Rep. 2017 Aug 29;20(9):2201-2214
pubmed: 28854368
Physiol Genomics. 2017 Nov 1;49(11):667-681
pubmed: 28939645
Oncotarget. 2017 Jun 29;8(38):63715-63723
pubmed: 28969023
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593