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| 1 | Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort显示文摘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 To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.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 E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap MS.RESULTS Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. Moreover,HRMAS analysis indicated that tumor tissue has altered metabolic features vs non-tumor counterparts, presenting increased levels of certain metabolites such as taurine and phosphocholine and lower levels of lactate. In proteomic experiments, we detected an enlarged number of proteins in tumors that are mainly implicated in basic biological functions like mitochondrial activity,DNA/RNA processing, vesicular trafficking, metabolism, cytoskeleton and splicing.CONCLUSION 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. | Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía Nú?ez María Fernández-Velasco Paloma Martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán Miguel ángel Peinado Lisardo Boscá | 2019 | World Journal of Gastroenterology2019，25，4： | 4 |
| 2 | Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice显示文摘 | Bego?a Cerdá Rafael Llorach José J. Cerón Juan Carlos Espín Francisco A. Tomás-Barberán | 2003 | European Journal of Nutrition2003，，1： | 2 |
| 3 | Survival benefit in critically ill burned patients receiving selective decontamination of the digestive traet显示文摘 | Miguel A de La Cal Enrique Cerd~t Paloma Garc ~ a-Hierro | 2005 | Ann Surg2005，204，3： | 1 |
| 4 | Effects of rock fragment cover on soil infiltration,interrill runoff and erosion显示文摘 | CerdàA | 2001 | European Journal of Soil Science2001，52，1： | 1 |
| 5 | Modification of the response of saline stressed tomato plants by the correction of cation disorders显示文摘 | Carvajal M Cerd A inez V M | 2000 | Plant Growth Regulation2000，，30： | 1 |
| 6 | Modalities of continuous renal replacement therapy:technical and clinical considerations显示文摘 | Cerd A Ronco C | | 0，，02： | 1 |
| 7 | The contrasting characteristics of acute kidney injury in developed and developing countries显示文摘 | Cerdá J Bagga A Kher V | | 0，，： | 1 |
| 8 | An MILP framework for batch reactive scheduling with limited discrete resources 显示文摘 | Mendez C A Cerd J | 2004 | Computers&Chemical Engineering2004，28，67： | 1 |
| 9 | A genotype-phenotype correlation study in a group of 54 patients with X-linked agammaglobulinemia 显示文摘 | L o pez-Granados E P o fez de Diego R Ferreira Cerd a n A | 2005 | J Allergy Clin Immunol2005，116，3： | 1 |
| 10 | The redox switch/ redox couplinghypothesis显示文摘 | Cerdán S Rodrigues TB Sierra A | 2006 | Neurochem Int2006，48，： | 1 |
| 11 | Study of the population structure of Haemophilus parasuis by multilocus sequence typing显示文摘 | Olvera A Cerdà-Cué11ar M Aragon V | 2006 | Microbiology2006，152，12： | 1 |
| 12 | State-of-the-art review of optimization methods for short-term scheduling of batch processes显示文摘 | Méndez C A Cerdá J Grossmann I E | 2006 | Computer & Chemical Engineering2006，30，67： | 1 |
| 13 | Soil water erosion on road embankments in eastern Spain显示文摘 | CERD(A) A | | 0，，： | 1 |
| 14 | Phylogenetic relationships and gene expression pattern of three different cathepsin L (Ctsl)isoforms in zebrafish: Ctsla is the putative yolk processing enzyme 显示文摘 | Tingaud-Sequeira A Cerd J | 2007 | Gene2007，386，12： | 1 |
| 15 | Optimal scheduling of batch plants satisfying multiple product orders with different due-dates显示文摘 | Henning G P Cerdá J | 2000 | Computers and Chemical Engineering2000，24，： | 1 |
| 16 | Optimal scheduling of a resource-constrained multiproduct batch plant supplying intermediates to nearby end-product facilities显示文摘 | Cerdá J | 2000 | Computers and Chemical Engineering2000，24，： | 1 |
| 17 | An MILP-based approach to the short-term scheduling of make-and-pack continuous production plants显示文摘 | MINDEZ C A CERD J | 2002 | OR Spec- trum2002，24，4： | 1 |
| 18 | Soil and water losses fi'om new citrus orchards growing on sloped soils in the western Mediterranean basin显示文摘 | Cerd/~ A Morera A G Bodi M B | 2009 | Earth Surface Proces- ses and Landforms2009，34，13： | 1 |
| 19 | Speciation analysis of inorganic arsenic by a multisyringe flow injection system with hydride generation- atomic fluorescence spectrometric detection 显示文摘 | Leal L O Forteza R Cerd'a V | 2006 | Talanta2006，69，： | 1 |
| 20 | First Highly Efficient and Photostable E and C Derivatives of 4,4‐Difluoro‐4‐bora‐3a,4a‐diaza‐ s ‐indacene (BODIPY) as Dye Lasers in the Liquid Phase, Thin Films, and Solid‐State Rods显示文摘 | Gonzalo Duran‐Sampedro Ixone Esnal Antonia R. Agarrabeitia Jorge Ba?uelos Prieto Luis Cerdán Inmaculada García‐Moreno Angel Costela I?igo Lopez‐Arbeloa María J. Ortiz | 2014 | Chem. Eur. J2014，，9： | 1 |
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