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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 | Reduced corneal thickness values in postmenopausal women with dry eye 显示文摘 | Sanchis-Gimeno JA Lleo-Perez A Alonso L | 2005 | Cornea2005，24，1： | 1 |
| 3 | High-performance liquid chromatography with amperometric detection applied to the screening of 1,4-dihydropyridines inhuman plasma显示文摘 | Lopez JA Martinez V Alonso RM | 2000 | Journal of Chromatography A2000，870，： | 1 |
| 4 | Ifos-famide encephalopathy and methylene-blue:a case report显示文摘 | Alonso JL Nieto Y López JA | 1996 | Ann Oncol1996，7，： | 1 |
| 5 | Lung collapse during low tidal volume ventilation in acute respiratory distress syndrome显示文摘 | Kallet RH Siobal MS Alonso JA | 2001 | Respir Care Med2001，46，1： | 1 |
| 6 | Use of the Gamma nail in the treatment of fracture of the proximal femur 显示文摘 | Valverde JA Alonso MG Porto JG | 1998 | Clin Orthop Relat Res1998，350，： | 1 |
| 7 | Health-related quality of life in Spanish women with osteoporosis 显示文摘 | Aranha LLM Miron Canelo JA Alonso Sardon M | 2006 | Rev Saude Publica2006，40，2： | 1 |
| 8 | Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome 显示文摘 | NUCKTON TJ ALONSO JA KALLET RH | 2002 | N Engl J Med2002，346，17： | 1 |
| 9 | Estrogens as neuropro- tectants against ischemic stroke显示文摘 | ALONSO DE LECIIANA M EGIDO JA | 2006 | Cerebrovasc Dis2006，21，2： | 1 |
| 10 | The beneficial impact of revision of Kasai portoenterostomy for biliary atresia:an institutional study显示文摘 | Bondoc AJ Taylor JA Alonso MH | 2012 | Ann Surg2012，255，3： | 1 |
| 11 | Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome 显示文摘 | Nuckton TJ Alonso JA Kallet RH | 2002 | N Engl J Med2002，346，17： | 1 |
| 12 | Use of the Gamma nail in the treatment of fracture of the proximal femur 显示文摘 | Valverde JA Alonso MG Porto JG | 1998 | Clin Orthop Related Res1998，，350： | 1 |
| 13 | Fast screening method for the determination of angiotensin Ⅱ receptor antagonists in human plasma by high - performance liquid chromatography with fluorimetric detection显示文摘 | Gonzalez L Lopez JA Alonso RM | 2002 | J Chromatogr A2002，949，1： | 1 |
| 14 | Processing of rab- bit hemorrhagic disease virus polyprotein 显示文摘 | Mart~n Alonso JM Casais R Boga JA | 1996 | J Virol1996，70，2： | 1 |
| 15 | Peculiarities of stroke risk in women显示文摘 | Egido JA Alonso de Lecinana M | 2007 | Cerebrovasc Dis2007，241，： | 1 |
| 16 | Lung collapse during low tidal volume ventilation in acute respiratory distress syndrome 显示文摘 | Kallet RH Siobal MS Alonso JA | 2001 | Respir Care2001，46，1： | 1 |
| 17 | Estrogens as neuroprotectants against ischemic stroke显示文摘 | Alonso de Leciana M Egido JA | 2006 | Cerebrovasc Dis2006，21，2： | 1 |
| 18 | Solid-phase extraction and high-performance liquid chromatography applied to the determination of quinapril and its metabolite quinaprilat in urine 显示文摘 | PRIETO JA ALONSO RM JIMENEZ RM | 2001 | J Chromatogr Sci2001，39，4： | 1 |
| 19 | Relation between resistivity and corrosion rate of reinforcements in carbonated mortar made with several cement types显示文摘 | Alonso C Andrade A Gonzalez JA | 1988 | Cement Concrete Res1988，8，： | 1 |
| 20 | A video-based tracking analysis to assess the chronic toxic effects of fluoride ion on the aquatic snail Pota- mopyrgus antipodarum (Hydrobiidae, Mollusca)显示文摘 | Alonso ~ Camargo JA | 2012 | Ecotoxicol En- viron Saf2012，81，： | 1 |
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