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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 | A role for radiotherapy in the management of advanced medullary thyroid carcinoma: the mayo clinic experience显示文摘 | Call JA Caudill JS Mclver B | 2013 | Rare Tumors2013，5，3： | 1 |
| 3 | Bevacizumab in combination with metronomic chemotherapy in patients with anthracyeline-and taxane-refractory breast cancer显示文摘 | Garcia-Saenz JA Martin M Calles A | 2008 | J Chemother2008，20，5： | 1 |
| 4 | A role for radiotherapy in the management of advanced medullary thyroid carcinoma: the mayo clinic experience显示文摘 | Call JA Caudill JS McIver B | 2013 | Rare Tumors2013，5，3： | 1 |
| 5 | Targeted manipulation of apoptosis in cancer treatment显示文摘 | Call JA Eckhardt SG Camidge DR | | 0，，10： | 1 |
| 6 | Immunopathology of a two-hit murine model of acid aspiration lung injury显示文摘 | Nemzek JA Call DR Ebong SJ | 2000 | Am J Physiol Lung Cell Mol Physiol2000，278，3： | 1 |
| 7 | Intensity- modulated Radiation Therapy for Anal Cancer: Results From a Multi-Institutional Retrospective Cohort Study 显示文摘 | Call JA Prendergast BM Jensen LG | 2014 | Am J Clin Oncol2014，，： | 1 |
| 8 | Impact of immediate versus delayed axillary node dissection on surgical outcomes in breast Cancer patients with positive sentinel nodes:results from American College of Surgeons Oncology Group Trials Z0010 and Z0011显示文摘 | Olson JA Jr Mc Call LM Beitsch P | 2008 | Clin Oncol2008，26，21： | 1 |
| 9 | Bevaeizumab in combination with metronomic chemotherapy in patients with an- thracycline - and taxane - refractory breast cancer 显示文摘 | Garcta - Sdenz JA Martn M Calles A | 2008 | Chemoth- er2008，20，5： | 1 |
| 10 | An outbreak of West Nile virus in a New York city captive wildlife population 显示文摘 | Calle PP Mangiafico JA | 2002 | Am J Trop Med Hyg2002，67，： | 1 |
| 11 | A role for radiothe-rapy in the management of advanced medullary thyroidcarcinoma:the mayo clinic experience显示文摘 | Call JA Caudill JS Mclver B | 2013 | Rare Tumors2013，5，3： | 1 |
| 12 | The effect of the III/V ratio and substrate temperature on the morphology and properties of GaN- and A1N-layers grown by molecular epitaxy on Si(111) 显示文摘 | SANCHEZ-GARCIA M A CALL MONROY M | 1998 | Journal of Crystal Growth1998，183，12： | 1 |
| 13 | Adaptivestrength gains in dystrophic muscle exposed to repeatedbouts of eccentric contraction显示文摘 | Call JA Eckhoff MD Baltgalvis KA | 2011 | J Appl Physiol2011，111，6： | 1 |
| 14 | Bevaci- metronomic chemotherapy in - and taxane - refractory breast cancer 显示文摘 | Garcia - Saenz JA Martin zumab in combination with patients with anthraeycline M Calles A | 2008 | J Chemother2008，20，5： | 1 |
| 15 | An outbreak of WestNile virus in a New York city captive wildlife population显示文摘 | Ludwig GV Calle PP Mangiafico JA | 2002 | Am JTrop Med Hyg2002，67，1： | 1 |
| 16 | Targeted manipulation of apoptosis in cancer treatment 显示文摘 | Call JA Eckhardt SG Camidge DR | 2008 | Lancet Oncol2008，9，： | 1 |
| 17 | Preliminary pharmacolog- ic and clinical evaluation of camptothecin sodium ( NSC-100880 ) 显示文摘 | Gottlieb JA Guarino AM Call JB | 1970 | Cancer Chemother Rcp1970，54，6： | 1 |
| 18 | A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain显示文摘 | Callén E Casado JA Tischkowitz MD | 2005 | Blood2005，105，5： | 1 |
| 19 | Bevacizumab in combination with metronomic chemotherapy in patients with anthracycline- and taxane -refractory breast cancer 显示文摘 | Garcia- Saenz JA Martin M Calles A | 2008 | J Chemother2008，20，5： | 1 |
| 20 | The effects of prednisolone on skeletal muscle contractility in mdx mice显示文摘 | Baltgalvis KA Call JA Nikas JB | 2009 | Muscle Nerve2009，40，3： | 1 |
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