RESUMO
Chronic pancreatitis is associated with impaired quality of life, high incidence of comorbidities, serious complications and mortality. Healthcare costs are exorbitant. Some medical societies have developed guidelines for treatment based on scientific evidence, but the gathered level of evidence for any individual topic is usually low and, therefore, recommendations tend to be vague or weak. In the present position papers on chronic pancreatitis from the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees we aimed at providing defined position statements for the clinician based on updated review of published literature and on multidisciplinary expert agreement. The final goal is to propose the use of common terminology and rational diagnostic/therapeutic circuits based on current knowledge. To this end 51 sections related to chronic pancreatitis were reviewed by 21 specialists from 6 different fields to generate 88 statements altogether. Statements were designed to harmonize concepts or delineate recommendations. Part 2 of these paper series discuss topics on treatment and follow-up. The therapeutic approach should include assessment of etiological factors, clinical manifestations and complications. The complexity of these patients advocates for detailed evaluation in multidisciplinary committees where conservative, endoscopic, interventional radiology or surgical options are weighed. Specialized multidisciplinary units of Pancreatology should be constituted. Indications for surgery are refractory pain, local complications, and suspicion of malignancy. Enzyme replacement therapy is indicated if evidence of exocrine insufficiency or after pancreatic surgery. Response should be evaluated by nutritional parameters and assessment of symptoms. A follow-up program should be planned for every patient with chronic pancreatitis.
Assuntos
Pancreatite Crônica , Qualidade de Vida , Seguimentos , Humanos , Pancreatite Crônica/complicações , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/terapia , Sociedades MédicasRESUMO
Chronic pancreatitis is a chronic fibroinflammatory disease of the pancreas with prevalence around 50 cases per 100,000 inhabitants. It appears to originate from diverse and yet mixed etiological factors. It shows highly variable presenting features, complication types and disease progression rates. Treatment options are as wide as the multiple personalized scenarios the disease might exhibit at a given time point. Some medical societies have developed guidelines for diagnosis and treatment based on scientific evidence. Although these efforts are to be acknowledged, the gathered level of evidence for any topic is usually low and, therefore, recommendations tend to be vague or weak. In the present series of position papers on chronic pancreatitis from the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees we aimed at providing defined position statements for the clinician based on updated review of published literature and on interdisciplinary expert agreement. The final goal is to propose the use of common terminology and rational diagnostic/therapeutic circuits based on current knowledge. To this end 51 sections related to chronic pancreatitis were reviewed by 21 specialists from 6 different fields to generate 88 statements altogether. Statements were designed to harmonize concepts or delineate recommendations. Part 1 of this paper series discusses topics on aetiology and diagnosis of chronic pancreatitis. Main clinical features are abdominal pain, exocrine and endocrine insufficiency and symptoms derived from complications. Some patients remain symptom-free. Diagnosis (definitive, probable or uncertain) should be based on objective data obtained from imaging, histology, or functional tests.
Assuntos
Pancreatite Crônica/diagnóstico , Pancreatite Crônica/etiologia , Diagnóstico Diferencial , Humanos , Cirrose Hepática/diagnóstico , Imageamento por Ressonância Magnética , Medição da Dor/métodos , Testes de Função Pancreática/métodos , Neoplasias Pancreáticas/diagnóstico , Pseudocisto Pancreático/diagnóstico , Pancreatite Crônica/patologia , Fatores de Risco , Sociedades Médicas , Espanha , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
INTRODUCTION: The socioeconomic burden of irritable bowel syndrome with constipation (IBS-C) has never been formally assessed in Spain. PATIENTS AND METHODS: This 12-month (6-month retrospective and prospective periods) observational, multicentre study assessed the burden of moderate-to-severe IBS-C in Spain. Patients were included if they had been diagnosed with IBS-C (Rome III criteria) within the last 5 years and had moderate-to-severe IBS-C (IBS Symptom Severity Scale score [IBS-SSS] ≥175) at inclusion. The primary objective was to assess the direct cost to the Spanish healthcare system (HS). RESULTS: A total of 112 patients were included, 64 (57%) of which had severe IBS-C at inclusion. At baseline, 89 (80%) patients reported abdominal pain and distention. Patient quality of life (QoL), measured by the IBS-C QoL and EQ-5D instruments, was found to be impaired with a mean score of 59 and 57 (0-100, worst-best), respectively. Over the 6-month prospective period the mean IBS-C severity, measured using the IBS-SSS showed some improvement (315-234 [0-500, best-worst]). During the year, 89 (80%) patients used prescription drugs for IBS-C, with laxatives being the most frequently prescribed (n=70; 63%). The direct cost to the HS was 1067, and to the patient was 568 per year. The total direct cost for moderate-to-severe IBS-C was 1635. DISCUSSION: The majority of patients reported continuous IBS-C symptoms despite that 80% were taking medication to treat their IBS-C. Overall healthcare resource use and direct costs were asymmetric, with a small group of patients consuming the majority of resources.
Assuntos
Constipação Intestinal/economia , Custos de Cuidados de Saúde , Síndrome do Intestino Irritável/economia , Dor Abdominal/etiologia , Constipação Intestinal/complicações , Constipação Intestinal/tratamento farmacológico , Custos Diretos de Serviços , Feminino , Dilatação Gástrica/etiologia , Fármacos Gastrointestinais/economia , Fármacos Gastrointestinais/uso terapêutico , Necessidades e Demandas de Serviços de Saúde/economia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Socioeconômicos , Espanha , Fatores de TempoRESUMO
Identifying biomarkers linked to pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP) is crucial for early detection, treatment, and prevention. Methods: Association analyses of 10 serological biomarkers involved in cell signalling (IFN-γ, IL-6, IL-8, IL-10), oxidative stress (superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities, total glutathione (GSH), malondialdehyde (MDA) levels), and intestinal permeability proteins (zonulin, I-FABP2) were conducted across PDAC (n = 12), CP (n = 21) and control subjects (n = 23). A Mendelian randomisation (MR) approach was used to assess causality of the identified significant associations in two large genetic cohorts (FinnGen and UK Biobank). Results: Observational results showed a downregulation of SOD and GPx antioxidant enzyme activities in PDAC and CP patients, respectively, and higher MDA levels in CP patients. Logistic regression models revealed significant associations between CP and SOD activity (OR = 0.21, 95% CI [0.05, 0.89], per SD), GPx activity (OR = 0.28, 95% CI [0.10, 0.79], per SD), and MDA levels (OR = 2.05, 95% CI [1.36, 3.08], per SD). MR analyses, however, did not support causality. Conclusions: These findings would not support oxidative stress-related biomarkers as potential targets for pancreatic diseases prevention. Yet, further research is encouraged to assess their viability as non-invasive tools for early diagnosis, particularly in pre-diagnostic CP populations.
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Currently, there are no reliable biomarkers for the diagnosis of pancreatic cancer (PaC). Glycoproteomic approaches that analyze the glycan determinants on specific glycoproteins have proven useful to develop more specific cancer biomarkers than the corresponding protein levels. In PaC, mesothelin (MSLN) is a neo-expressed glycoprotein. MSLN glycosylation has not been described and could be altered in PaC. In this work, we aimed to characterize MSLN glycans from PaC cells and serum samples to assess their potential usefulness as PaC biomarkers. First, we analyzed MSLN glycans from PaC cell lines and then we developed an enzyme-linked lectin assay to measure core fucosylated-MSLN (Cf-MSLN) glycoforms. MSLN glycans from PaC cells were analyzed by glycan sequencing and through Western blotting with lectins. All of the cell lines secreted MSLN, with its three N-glycosylation sites occupied by complex-type N-glycans, which were mainly α2,3-sialylated, core fucosylated and highly branched. The Cf-MSLN glycoforms were quantified on PaC serum samples, and compared with MSLN protein levels. The Cf-MSLN was significantly decreased in PaC patients compared to control sera, while no differences were detected by using MSLN protein levels. In conclusion, Cf-MSLN glycoforms were differently expressed in PaC, which opens the way to further investigate their usefulness as PaC biomarkers.
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Chronic pancreatitis tends to develop a number of complications that may constitute the form of presentation of the disease. Some societies have issued guidelines for diagnosis and treatment of chronic pancreatitis complications, but the level of evidence for any topic is usually low and recommendations tend to be weak. We aimed at providing defined position statements for the clinician based on updated review of published literature and on multidisciplinary expert agreement. The goal was to propose defined terminology and rational diagnostic/therapeutic circuits based on current knowledge. To this end 14 sections related to complications and special forms of chronic pancreatitis (early chronic, groove and autoimmune pancreatitis) were reviewed by 21 specialists from 6 different fields to generate 32 statements. Featured statements assert common bile duct stenosis does not require invasive treatment (endoscopic or surgical) unless cholestasis, cholangitis, lithiasis or other symptoms develop. Pancreatic duct strictures and calculi should be approached (after ruling out malignancy) if causing pain, pancreatitis, pseudocysts or other complications. Treatment of symptomatic pseudocysts must be individualized, considering associated main duct stenosis, vascular and pericystic complications. Higher risk conditions for pancreatic cancer are advance age, smoking, genetic background, recent diagnosis of chronic pancreatitis or diabetes, and appearance of new symptoms. Groove pancreatitis can initially be treated with conservative measures. Both prednisolone or rituximab can induce remission and maintenance of autoimmune pancreatitis. Internal fistula, vascular complications, bacterial overgrowth, osteoporosis and renal lithiasis require specific therapeutic approaches.
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Histoplasmosis is an endemic mycosis in some areas of North and South America. This disease is usually asymptomatic, but it can result in severe and disseminated infection involving gastrointestinal tract, especially in immunocompromised individuals. We report a case of a 33-years-old Ecuadorian male treated with infliximab who developed disseminated histoplasmosis with gastrointestinal affection. Due to the non-specific presentation of gastrointestinal histoplasmosis, the diagnosis is often delayed and it causes poor outcomes. It is important to consider this diagnosis in immunocompromised patients with compatible symptoms, like patients on TNF inhibitors.
Assuntos
Histoplasmose , Adulto , Trato Gastrointestinal , Histoplasmose/induzido quimicamente , Histoplasmose/diagnóstico , Humanos , Hospedeiro Imunocomprometido , Infliximab/efeitos adversos , MasculinoRESUMO
2-DE is broadly used for quantitative analysis of differential protein expression in complex mixtures such as serum samples or cell lysates. PTMs directly influence the 2-DE pattern, and knowledge of the rules of protein separation is required in order to understand the protein distribution in a 2-DE gel. Glycosylation is the most common PTM and can modify both the molecular weight and the pI of a protein. In particular, the effect of charged monosaccharides (mainly sialic acids, SAs) on the 2-DE pattern of a protein is of major interest since changes in sialylation are regularly observed in comparative studies. Little is known about the pI shift of a glycoprotein induced by the presence of SAs, or whether this shift is the same for all glycoproteins. To address this issue, this study examined the influence of SA on the 2-DE pattern of three serum glycoproteins (haptoglobin, α1-antitrypsin and ribonuclease 1), which N-glycan chains had been previously characterised, and reviewed existing bibliographic data. The SA content of the different glycoforms of a glycoprotein showed a negative linear correlation with the pI, although the slope varied among the studied glycoproteins. We also described a positive correlation between the protein pI and the pI decrease per SA molecule.
Assuntos
Eletroforese em Gel Bidimensional/métodos , Glicoproteínas/química , Ácido N-Acetilneuramínico/química , Adenocarcinoma/metabolismo , Algoritmos , Glicoproteínas/metabolismo , Glicosilação , Haptoglobinas/química , Haptoglobinas/metabolismo , Humanos , Ponto Isoelétrico , Modelos Lineares , Modelos Químicos , Neoplasias Pancreáticas/metabolismo , Pancreatite Crônica/metabolismo , Ribonuclease Pancreático/sangue , Ribonuclease Pancreático/química , Ribonuclease Pancreático/metabolismo , alfa 1-Antitripsina/sangue , alfa 1-Antitripsina/química , alfa 1-Antitripsina/metabolismoRESUMO
Relative quantification of human alpha-acid glycoprotein (hAGP) glycan isomers using [12C6]/[13C6]-aniline in combination with multivariate data analysis is proposed as an efficient method for the identification of pancreatic ductal adenocarcinoma (PDAC) glycan biomarkers in serum samples. Intact and desialylated glycans from hAGP, purified from serum samples of patients with PDAC and chronic pancreatitis (ChrP), were labeled with aniline and analyzed by µZIC-HILIC-MS. Afterwards, partial least squares discriminant analysis (PLS-DA) was applied to the relative areas obtained for all glycan isomers in the different samples: pathological (ChrP or PDAC) versus healthy samples. Seven intact glycan isomers with α2-6 linked sialic acids, five of them also fucosylated, were the most meaningful to distinguish between PDAC and ChrP patients. The desialylated glycan isomers also identified by PLS-DA as potential biomarker candidates confirmed that antenna but also core fucosylation could be involved in PDAC. The analysis of intact and desialylated glycan isomers in combination with the multivariate data analysis revealed that the triantennary glycan with two fucoses of hAGP could have in the future a relevant role in the differentiation of patients with PDAC from those with ChrP. SIGNIFICANCE: Multivariate data analysis is currently being used in many omics fields for biomarker discovery. However, to date, no glycomics studies have applied chemometric tools combined with mass spectrometry in a preclinical research. In this work, this methodology has been used to identify altered glycosylation of human alpha-acid glycoprotein in pancreatic ductal adenocarcinoma (PDAC). The obtained results reveal that the triantennary glycan with two fucoses could have a great biomarker potential as it was relevant to differentiate PDAC and chronic pancreatitis (ChrP) patients.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Idoso , Carcinoma Ductal Pancreático/patologia , Feminino , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Pancreatite Crônica/metabolismo , Pancreatite Crônica/patologia , Neoplasias PancreáticasRESUMO
BACKGROUND: There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. METHODS: CA 19-9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. RESULTS: The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. CONCLUSIONS: Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/diagnóstico , Icterícia Obstrutiva/etiologia , Neoplasias Pancreáticas/diagnóstico , Pancreatite Crônica/diagnóstico , Idoso , Área Sob a Curva , Bilirrubina/sangue , Proteína C-Reativa/análise , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/fisiopatologia , Diagnóstico Diferencial , Testes Diagnósticos de Rotina , Feminino , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Icterícia Obstrutiva/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/fisiopatologia , Pancreatite Crônica/sangue , Curva ROC , Sensibilidade e Especificidade , Albumina Sérica/análiseRESUMO
Pancreatic cancer (PDAC) lacks reliable diagnostic biomarkers and the search for new biomarkers represents an important challenge. Previous results looking at a small cohort of patients showed an increase in α-1-acid glycoprotein (AGP) fucosylation in advanced PDAC using N-glycan sequencing. Here, we have analysed AGP glycoforms in a larger cohort using several analytical techniques including mass spectrometry (MS), capillary zone electrophoresis (CZE) and enzyme-linked lectin assays (ELLAs) for determining AGP glycoforms which could be PDAC associated. AGP from 31 serum samples, including healthy controls (HC), chronic pancreatitis (ChrP) and PDAC patients, was purified by immunoaffinity chromatography. Stable isotope labelling of AGP released N-glycans and their analysis by zwitterionic hydrophilic interaction capillary liquid chromatography electrospray MS (µZIC-HILIC-ESI-MS) showed an increase in AGP fucosylated glycoforms in PDAC compared to ChrP and HC. By CZE-UV analysis, relative concentrations of some of the AGP isoforms were found significantly different compared to those in PDAC and HC. Finally, ELLAs using Aleuria aurantia lectin displayed a significant increase in AGP fucosylation, before and after AGP neuraminidase treatment, in advanced PDAC compared to ChrP and HC, respectively. Altogether, these results indicate that α1-3 fucosylated glycoforms of AGP are increased in PDAC and could be potentially regarded as a PDAC biomarker.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/metabolismo , Proteínas de Neoplasias/sangue , Orosomucoide/metabolismo , Neoplasias Pancreáticas/metabolismo , Idoso , Sequência de Aminoácidos , Carcinoma Ductal Pancreático/diagnóstico , Feminino , Fucose/sangue , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Neoplasias Pancreáticas/diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
In this work we demonstrate the potential of glycan reductive isotope labeling (GRIL) using [(12)C]- and [(13)C]-coded aniline and zwitterionic hydrophilic interaction capillary liquid chromatography electrospray mass spectrometry (µZIC-HILIC-ESI-MS) for relative quantitation of glycosylation variants in selected glycoproteins present in samples from cancer patients. Human α1-acid-glycoprotein (hAGP) is an acute phase serum glycoprotein whose glycosylation has been described to be altered in cancer and chronic inflammation. However, it is not clear yet whether some particular glycans in hAGP can be used as biomarker for differentiating between these two pathologies. In this work, hAGP was isolated by immunoaffinity chromatography (IAC) from serum samples of healthy individuals and from those suffering chronic pancreatitis and different stages of pancreatic cancer, respectively. After de-N-glycosylation, relative quantitation of the hAGP glycans was carried out using stable isotope labeling and µZIC-HILIC-ESI-MS analysis. First, protein denaturing conditions prior to PNGase F digestion were optimized to achieve quantitative digestion yields, and the reproducibility of the established methodology was evaluated with standard hAGP. Then, the proposed method was applied to the analysis of the clinical samples (control vs. pathological). Pancreatic cancer samples clearly showed an increase in the abundance of fucosylated glycans as the stage of the disease increases and this was unlike to samples from chronic pancreatitis. The results gained here indicate the mentioned glycan in hAGP as a candidate structure worth to be corroborated by an extended study including more clinical cases; especially those with chronic pancreatitis and initial stages of pancreatic cancer. Importantly, the results demonstrate that the presented methodology combining an enrichment of a target protein by IAC with isotope coded relative quantitation of N-glycans can be successfully used for targeted glycomics studies. The methodology is assumed being suitable as well for other such studies aimed at finding novel cancer associated glycoprotein biomarkers.
Assuntos
Orosomucoide/química , Polissacarídeos/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Biomarcadores/sangue , Cromatografia de Afinidade , Cromatografia Líquida de Alta Pressão , Glicosilação , Humanos , Interações Hidrofóbicas e Hidrofílicas , Marcação por Isótopo , Nitrogênio/química , Orosomucoide/isolamento & purificação , Orosomucoide/metabolismo , Neoplasias Pancreáticas/patologia , Polissacarídeos/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray/instrumentaçãoRESUMO
Pancreatic adenocarcinoma (PDAC) usually shows an enhanced expression of sialyl-Lewis X (sLe(x)) and related epitopes. PDAC may secrete some of the proteins carrying such increased sLe(x) determinant into serum, so they could be used as PDAC markers. Previously, we identified acute-phase proteins with increased sLe(x) in both PDAC and in chronic pancreatitis patients. In this study, depleted sera from the main acute-phase proteins has been analysed for the search of proteins with increased sLe(x) levels in PDAC. Sera from healthy controls, chronic pancreatitis and PDAC patients were depleted, electrophoresed and subjected to sLe(x) immunodetection. Proteins that differentially expressed sLe(x) in PDAC were trypsin digested and identified by LC-ESI-QTOF mass spectrometry. Five protein bands that differentially expressed sLe(x) in PDAC were identified and corresponded to seven different acute-phase proteins. Among them, ceruloplasmin (CP) was selected for further analysis. N-glycan sequencing of CP confirmed the increase of sLe(x) levels in CP in PDAC patients. Healthy controls, chronic pancreatitis and PDAC patients' sera were immunoprecipitated with anti-CP antibodies, and their sLe(x) and CP levels were analysed by western blot. The sLe(x)/CP ratio tended to be higher for the PDAC group, which altogether suggests that the sLe(x)/CP ratio could be a useful biomarker for PDAC.
Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Ceruloplasmina/metabolismo , Oligossacarídeos/sangue , Neoplasias Pancreáticas/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Pancreatite Crônica/sangue , Polissacarídeos/química , Polissacarídeos/metabolismo , Antígeno Sialil Lewis XRESUMO
PURPOSE: Glycosylation of acute-phase proteins (APP), which is partially regulated by cytokines, may be distinct in disease and provide useful tumour markers. Thus, we have examined the glycosylation of major serum APP in pancreatic cancer (PaC), chronic pancreatitis (CP) and control patients. EXPERIMENTAL DESIGN: Using a specific anti-sialyl Lewis X antibody and N-glycan sequencing, we have determined glycosylation changes on α-1-acid glycoprotein (AGP), haptoglobin (HPT), fetuin (FET), α-1-antitrypsin (AT) and transferrin (TRF). RESULTS: Increased levels of sialyl Lewis X (SLe(x) ) were detected on AGP in advanced PaC and CP and on HPT, FET, AT and TRF in CP. An increase in N-glycan branching was detected on AGP and HPT in the advanced stage of PaC and CP and on FET and TRF in the CP. A core fucosylated structure was increased on AGP and HPT only in the advanced PaC patients. CONCLUSIONS AND CLINICAL RELEVANCE: Changes in APP SLe(x) and branching are probably associated with an inflammatory response because they were detected in both advanced PaC and CP patients and these conditions give rise to inflammation. On the contrary, the increase in APP core fucosylation could be cancer associated and the presence of this glycoform may give an advantage to the tumour.
Assuntos
Proteínas de Fase Aguda/metabolismo , Fígado/fisiopatologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/fisiopatologia , Pancreatite Crônica/metabolismo , Pancreatite Crônica/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Feminino , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Human pancreatic ribonuclease 1 (RNase 1) is a glycoprotein expressed mainly by the pancreas and also found in endothelial cells. The diagnosis of pancreatic cancer (PaC) remains difficult and therefore the search for sensitive and specific markers is required. Previous studies showed that RNase 1 from human healthy pancreas contained only neutral glycans, whereas RNase 1 from PaC cell lines contained sialylated structures. To determine whether these glycan tumor cell-associated changes were also characteristic of serum RNase 1 and could be used as a marker of PaC, we have analyzed the glycosylation of serum RNase 1. The origin of serum RNase 1 was also investigated. Serum RNase 1 from two PaC patients and two controls was purified and the glycans analyzed by high-performance liquid chromatography (HPLC)-based sequencing and mass spectrometry. Although normal and tumor serum RNase 1 contained the same glycan structures, there was an increase of 40% in core fucosylation in the main sialylated biantennary glycans in the PaC serum RNase 1. This change in proportion would be indicative of a subset of tumor-associated glycoforms of RNase 1, which may provide a biomarker for PaC. Two-dimensional electrophoresis of the RNase 1 from several endothelial cell lines, EA.hy926, human umbilical vein endothelial cells (HUVEC), human mammary microvessel endothelial cells (HuMMEC), and human lung microvessel endothelial cells (HuLEC), showed basically the same pattern and was also very similar to that of serum RNase 1. RNase 1 from EA.hy926 was then purified and presented a glycosylation profile very similar to that from serum RNase 1, suggesting that endothelial cells are the main source of this enzyme.