Serum biomarkers for the differentiation of autoimmune pancreatitis from pancreatic ductal adenocarcinoma

Autoimmune pancreatitis (AIP), a chronic inflammation caused by the immune system attacking the pancreas, usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma (PDAC). Serum biomarkers, substances that quantitatively change in sera during disease development, are a promising non-invasive tool with high utility for differentiating between these diseases. In this way, the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4 (IgG4) antibody are elevated. However, this approach has some drawbacks. Notably, IgG4 antibody concentrations are also elevated in sera from some patients with PDAC. This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC, evaluating the usefulness of immunoglobulins, autoantibodies, chemokines, and cytokines. The proposed serum biomarkers have proven useful, although most studies had a small sample size, did not examine their presence in patients with PDAC, or did not test them in humans. In addition, current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity, either alone or i

Serum nuclear magnetic resonance metabolomics analysis of human metastatic colorectal cancer: Biomarkers and pathway analysis

Junta de Andalucía, Grant/Award Numbers: 102C2000004, UAL2020-AGR-B1781, P20_01041; Gobierno de España, Grant/Award Numbers: PDC2021– 121248-I00, PLEC2021–007774; Instituto de Salud Carlos III (ISCIII), Grant/Award Number: PI19/01478; CTS-107 and FQM-376 groupsWe describe the use of nuclear magnetic resonance metabolomics to analyze blood serum samples from healthy individuals (n = 26) and those with metastatic colorectal cancer (CRC; n = 57). The assessment, employing both linear and nonlinear multivari- ate data analysis techniques, revealed specific metabolite changes associated with metastatic CRC, including increased levels of lactate, glutamate, and pyruvate, and decreased levels of certain amino acids and total fatty acids. Biomarker ratios such as glutamate-to-glutamine and pyruvate-to-alanine were also found to be related to CRC. The study also found that glutamate was linked to progression-free survival and that both glutamate and 3-hydroxybutyrate were risk factors for metastatic CRC. Additionally, gas chromatography coupled to flame-ionization detection was utilized to analyze the fatty acid profile and pathway analysis was performed on the profiled metabolites to understand the metabolic processes involved in CRC. A correlation was also found between the presence of certain metabolites in the blood of CRC patients and certain clinical features.Junta de Andalucia 102C2000004, UAL2020-AGR-B1781, P20_01041Gobierno de España MCIN/AEI/10.13039/501100011033/Unión Europea “Next GenerationEU”/PRTR (PDC2021–121248-I00 and PLEC2021–007774)Instituto de Salud Carlos III (ISCIII) (PI19/01478) (FEDER)CTS-107FQM-37

Tissue Specific Promoters in Colorectal Cancer

Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.This research was funded by FEDER, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I), and Instituto de Salud Carlos III (FIS), through projects PI11/01862 and PI11/0257

Chronic pancreatitis: analysis of disease progression factors

Background: Alcohol and tobacco are important risk factors for chronic pancreatitis (CP). Aim: To analyze the effect of etiological factors such as tobacco and alcohol and pancreatic enzyme replacement therapy (PERT) in the progression of CP. Material and Methods: Patients with a diagnosis of CP were recruited and grouped according to variables such as tobacco, alcohol and PERT. They were followed for 18 months. Subsequently, different variables and analytical parameters involved in the progression of the disease were analyzed. Results: A total of 50 patients diagnosed with CP were included. Of these, 28 patients underwent PERT, 39 were smokers and 33 were alcohol users. Compared with patients without PERT, those with PERT had a higher proportion of diabetes (64 and 32%, respectively), had a higher need for endoscopic treatment (25 and 0%, respectively) and a normal body mass index (71 and 27.3%, respectively. The smokers had higher calcium levels and increased lymphocytosis and leukocytosis. The alcohol consumption group had a higher mean age (p = 0.04) Conclusions: PERT may improve the nutritional status but does not reduce the need for endoscopic or surgical treatment. Smoking and alcohol consumption favored the progression of CP. Also, smoking induced a pro-inflammatory state.Fondos FEDER, A-CTS-436-UGR2

Liquid biopsy approach to pancreatic cancer

Supported by Junta de Andalucia, No. PC-0498-2017 and No. PC-0549-2017.Pancreatic cancer (PC) continues to pose a major clinical challenge. There has been little improvement in patient survival over the past few decades, and it is projected to become the second leading cause of cancer mortality by 2030. The dismal 5-year survival rate of less than 10% after the diagnosis is attributable to the lack of early symptoms, the absence of specific biomarkers for an early diagnosis, and the inadequacy of available chemotherapies. Most patients are diagnosed when the disease has already metastasized and cannot be treated. Cancer interception is vital, actively intervening in the malignization process before the development of a full-blown advanced tumor. An early diagnosis of PC has a dramatic impact on the survival of patients, and improved techniques are urgently needed to detect and evaluate this disease at an early stage. It is difficult to obtain tissue biopsies from the pancreas due to its anatomical position; however, liquid biopsies are readily available and can provide useful information for the diagnosis, prognosis, stratification, and follow-up of patients with PC and for the design of individually tailored treatments. The aim of this review was to provide an update of the latest advances in knowledge on the application of carbohydrates, proteins, cell-free nucleic acids, circulating tumor cells, metabolome compounds, exosomes, and platelets in blood as potential biomarkers for PC, focusing on their clinical relevance and potential for improving patient outcomes.Junta de Andaluci

Discovery of Pancreatic Adenocarcinoma Biomarkers by Untargeted Metabolomics

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal cancers, with a 5-year survival rate of less than 5%. In fact, complete surgical resection remains the only curative treatment. However, fewer than 20% of patients are candidates for surgery at the time of presentation. Hence, there is a critical need to identify diagnostic biomarkers with potential clinical utility in this pathology. In this context, metabolomics could be a powerful tool to search for new robust biomarkers. Comparative metabolomic profiling was performed in serum samples from 59 unresectable PDAC patients and 60 healthy controls. Samples were analyzed by using an untargeted metabolomics workflow based on liquid chromatography, coupled to high-resolution mass spectrometry in positive and negative electrospray ionization modes. Univariate and multivariate analysis allowed the identification of potential candidates that were significantly altered in PDAC patients. A panel of nine candidates yielded excellent diagnostic capacities. Pathway analysis revealed four altered pathways in our patients. This study shows the potential of liquid chromatography coupled to high-resolution mass spectrometry as a diagnostic tool for PDAC. Furthermore, it identified novel robust biomarkers with excellent diagnostic capacities.This research was funded by JUNTA DE ANDALUCIA, grant number PIN-0474-2016 and PC-0549-2017 and INSTITUTO DE SALUD CARLOS III (FEDER), grant number DTS17/00081

Role of Exocrine and Endocrine Insufficiency in the Management of Patients with Chronic Pancreatitis

Background: Exocrine pancreatic insufficiency results from the destruction of the pancreatic parenchyma and is diagnosed by using direct or indirect tests, both of which have shortcomings. Chronic pancreatitis is the most frequent cause of this pathology in adults. Methods: Patients meeting radiological or histological diagnostic criteria of chronic pancreatitis are enrolled and the stool elastase test is conducted, considering fecal elastase levels >200 µg/g to represent normal pancreatic function, and levels <200 µg/g to indicate the presence of exocrine pancreatic insufficiency. Additionally, we determine the body mass index of the patients and study their nutritional status and main biochemical and hematological variables, including their glucose and hemoglobin A1c (HbA1c) levels. Results: Exocrine pancreatic insufficiency is detected in 60% of the patients. Among these, 83.3% are severe cases, and 72% of the latter also are diagnosed with endocrine pancreatic insufficiency (diabetes mellitus). During the nutritional status study, HbA1c levels are significantly higher, and magnesium and prealbumin levels are significantly lower in patients with exocrine pancreatic insufficiency than in those without this disease. Conclusions: Exocrine and endocrine pancreatic insufficiency are highly prevalent among patients with chronic pancreatitis and an early diagnosis of these diseases is vital to improve the clinical management of these patients and reduce their risk of mortality.Junta de Andalucia PC-0549-2017 PC-0498-201

Leukemia multiclass assessment and classification from Microarray and RNA-seq technologies integration at gene expression level

In more recent years, a significant increase in the number of available biological experiments has taken place due to the widespread use of massive sequencing data. Furthermore, the continuous developments in the machine learning and in the high performance computing areas, are allowing a faster and more efficient analysis and processing of this type of data. However, biological information about a certain disease is normally widespread due to the use of different sequencing technologies and different manufacturers, in different experiments along the years around the world. Thus, nowadays it is of paramount importance to attain a correct integration of biologically-related data in order to achieve genuine benefits from them. For this purpose, this work presents an integration of multiple Microarray and RNA-seq platforms, which has led to the design of a multiclass study by collecting samples from the main four types of leukemia, quantified at gene expression. Subsequently, in order to find a set of differentially expressed genes with the highest discernment capability among different types of leukemia, an innovative parameter referred to as coverage is presented here. This parameter allows assessing the number of different pathologies that a certain gen is able to discern. It has been evaluated together with other widely known parameters under assessment of an ANOVA statistical test which corroborated its filtering power when the identified genes are subjected to a machine learning process at multiclass level. The optimal tuning of gene extraction evaluated parameters by means of this statistical test led to the selection of 42 highly relevant expressed genes. By the use of minimum- Redundancy Maximum-Relevance (mRMR) feature selection algorithm, these genes were reordered and assessed under the operation of four different classification techniques. Outstanding results were achieved by taking exclusively the first ten genes of the ranking into consideration. Finally, specific literature was consulted on this last subset of genes, revealing the occurrence of practically all of them with biological processes related to leukemia. At sight of these results, this study underlines the relevance of considering a new parameter which facilitates the identification of highly valid expressed genes for simultaneously discerning multiple types of leukemia.This work was supported by Project TIN2015-71873-R (Spanish Ministry of Economy and Competitiveness -MINECO- and the European Regional Development Fund -ERDF) and Junta de Andalucı´a (P12–TIC–2082)

Prognostic value of RT-PCR tyrosinase detection in peripheral blood of melanoma patients

Malignant melanoma (MM) prognosis has been related to tumour thickness and clinical stage and metastasis risk has been associated with presence of tumour cells in peripheral blood. The aim of this study was to determine the relationship between presence of tyrosinase in peripheral blood of MM patients and their clinical prognosis. Blood samples from 58 MM patients (stage I–IV) were analysed, using RT-PCR assay to detect tyrosinase mRNA. The results showed that positive RT-PCR assay for tyrosinase were significantly associated with clinical status and tumour thickness. After a median follow-up of 24 months, RT-PCR results were found to be significant correlated with recurrence (p < 0.05) and clinical stage III (p < 0.05). Separate analysis of stage III tumours to determine the prognostic value of tyrosinase presence in peripheral blood showed an overall 24-month survival rate of 70% in the RT-PCR negative group versus 10% in the positive group (p < 0.02). These results suggest that detection of circulating melanoma cells may be especially relevant in stage III patients, in whom RT-PCR positivity defines a subpopulation at high risk of recurrence.This study was supported by the Fondo de Investigación Sanitaria de la Seguridad Social (FIS), Spain through no. PI041372