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4. Quantification of rare somatic single nucleotide variants by droplet digital PCR using SuperSelective primers

Author

Pablo-Fontecha, Verónica, Hernández-Illán, Eva, Reparaz, Andrea, Asensio, Elena, Morata, Jordi, Tonda, Raúl, Lahoz, Sara, Parra, Carolina, Lozano, Juan José, García-Heredia, Anabel, Martínez-Roca, Alejandro, Beltran, Sergi, Balaguer, Francesc, Jover, Rodrigo, Castells, Antoni, Trullàs, Ramon, Podlesniy, Petar, and Camps, Jordi

Published
2023
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7. Metabolic adaptations in severe obesity: Insights from circulating oxylipins before and after weight loss

Author

Jiménez-Franco, Andrea, Castañé, Helena, Martínez-Navidad, Cristian, Placed-Gallego, Cristina, Hernández-Aguilera, Anna, Fernández-Arroyo, Salvador, Samarra, Iris, Canela-Capdevila, Marta, Arenas, Meritxell, Zorzano, Antonio, Hernández-Alvarez, María Isabel, Castillo, Daniel del, Paris, Marta, Menendez, Javier A., Camps, Jordi, and Joven, Jorge

Published
2024
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9. Mitochondrial RNA methyltransferase TRMT61B is a new, potential biomarker and therapeutic target for highly aneuploid cancers

Author

Martín, Alberto, Epifano, Carolina, Vilaplana-Marti, Borja, Hernández, Iván, Macías, Rocío I. R., Martínez-Ramírez, Ángel, Cerezo, Ana, Cabezas-Sainz, Pablo, Garranzo-Asensio, Maria, Amarilla-Quintana, Sandra, Gómez-Domínguez, Déborah, Caleiras, Eduardo, Camps, Jordi, Gómez-López, Gonzalo, Gómez de Cedrón, Marta, Ramírez de Molina, Ana, Barderas, Rodrigo, Sánchez, Laura, Velasco-Miguel, Susana, and Pérez de Castro, Ignacio

Published
2023
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16. Preliminary Metabolomics Study Suggests Favorable Metabolic Changes in the Plasma of Breast Cancer Patients after Surgery and Adjuvant Treatment.

Author

Jiménez-Franco, Andrea, Jiménez-Aguilar, Juan Manuel, Canela-Capdevila, Marta, García-Pablo, Raquel, Castañé, Helena, Martínez-Navidad, Cristian, Araguas, Pablo, Malavé, Bárbara, Benavides-Villarreal, Rocío, Acosta, Johana C., Onoiu, Alina Iuliana, Somaiah, Navita, Camps, Jordi, Joven, Jorge, and Arenas, Meritxell

Subjects
AMINO acid metabolism, METABOLIC reprogramming, CANCER chemotherapy, ENERGY metabolism, CANCER treatment
Abstract

Background/Objectives: The management of early breast cancer (BC) includes surgery, followed by adjuvant radiotherapy, chemotherapy, hormone therapy, or immunotherapy. However, the influence of these interventions in metabolic reprogramming remains unknown. This study explored alterations in the plasma metabolome of BC patients following distinct treatments to deepen our understanding of BC pathophysiology, outcomes, and the identification of potential biomarkers. Methods: We included 52 women diagnosed with BC and candidates for surgery as primary oncological treatment. Blood samples were collected at diagnosis, two weeks post-surgery, and one month post-radiotherapy. Plasma samples from 49 healthy women served as controls. Targeted metabolomics assessed 74 metabolites spanning carbohydrates, amino acids, lipids, nucleotide pathways, energy metabolism, and xenobiotic biodegradation. Results: Before treatment, the BC patients exhibited notable changes in carbohydrate, nucleotide, lipid, and amino acid metabolism. We noticed a gradual restoration of specific metabolite levels (hypoxanthine, 3-phosphoglyceric acid, xylonic acid, and maltose) throughout different treatments, suggesting a normalization of the nucleotide and carbohydrate metabolic pathways. Moreover, we observed increased dodecanoic acid concentrations, a metabolite associated with cancer protection. These variations distinguished patients from controls with high specificity and sensitivity. Conclusions: Our preliminary study suggests that oncological treatments modify the metabolism of patients towards a favorable profile with a decrease in the pathways that favor cell proliferation and an increase in the levels of anticancer molecules. These findings emphasize the pivotal role of metabolomics in recognizing the biological pathways influenced by each cancer treatment and the resulting metabolic consequences. Furthermore, it aids in identifying potential biomarkers for disease onset and progression. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Combining Metabolomics and Machine Learning to Identify Diagnostic and Prognostic Biomarkers in Patients with Non-Small Cell Lung Cancer Pre- and Post-Radiation Therapy.

Author

Murcia-Mejía, Mauricio, Canela-Capdevila, Marta, García-Pablo, Raquel, Jiménez-Franco, Andrea, Jiménez-Aguilar, Juan Manuel, Badía, Joan, Benavides-Villarreal, Rocío, Acosta, Johana C., Arguís, Mónica, Onoiu, Alina-Iuliana, Castañé, Helena, Camps, Jordi, Arenas, Meritxell, and Joven, Jorge

Subjects
STEREOTACTIC radiotherapy, NON-small-cell lung carcinoma, RECEIVER operating characteristic curves, PROGNOSIS, CANCER radiotherapy
Abstract

Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases and poor prognosis in advanced stages. This study explored shifts in circulating metabolite levels in NSCLC patients versus healthy controls and examined the effects of conventionally fractionated radiation therapy (CFRT) and stereotactic body radiation therapy (SBRT). We enrolled 91 NSCLC patients (38 CFRT and 53 SBRT) and 40 healthy controls. Plasma metabolite levels were assessed using semi-targeted metabolomics, revealing 32 elevated and 18 reduced metabolites in patients. Key discriminatory metabolites included ethylmalonic acid, maltose, 3-phosphoglyceric acid, taurine, glutamic acid, glycocolic acid, and d-arabinose, with a combined Receiver Operating Characteristics curve indicating perfect discrimination between patients and controls. CFRT and SBRT affected different metabolites, but both changes suggested a partial normalization of energy and amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures in NSCLC patients with potential as diagnostic biomarkers. The differing metabolic responses to CFRT and SBRT reflect their unique therapeutic impacts, underscoring the utility of this technique in enhancing NSCLC diagnosis and treatment monitoring. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Serum Levels of Arachidonic Acid, Interleukin-6, and C-Reactive Protein as Potential Indicators of Pulmonary Viral Infections: Comparative Analysis of Influenza A, Respiratory Syncytial Virus Infection, and COVID-19.

Author

Iftimie, Simona, Gabaldó-Barrios, Xavier, Penadés-Nadal, Joan, Canela-Capdevila, Marta, Piñana, Rubén, Jiménez-Franco, Andrea, López-Azcona, Ana F., Castañé, Helena, Cárcel, María, Camps, Jordi, Castro, Antoni, and Joven, Jorge

Subjects
RESPIRATORY syncytial virus infections, RESPIRATORY infections, VIRUS diseases, ARACHIDONIC acid, COMMUNICABLE diseases
Abstract

Acute respiratory tract infections, including influenza A (FluA), respiratory syncytial virus (RSV) infection, and COVID-19, can aggravate to levels requiring hospitalization, increasing morbidity and mortality. Identifying biomarkers for an accurate diagnosis and prognosis of these infections is a clinical need. We performed a cross-sectional study aimed to investigate the changes in circulating levels of arachidonic acid, interleukin 6 (IL-6), and C-reactive protein (CRP) in patients with FluA, RSV, or COVID-19, and to analyze the potential of these parameters as diagnosis or prognosis biomarkers. We analyzed serum samples from 172 FluA, 80 RSV, and 217 COVID-19 patients, and 104 healthy volunteers. Individuals with lung viral diseases showed reduced arachidonic acid concentrations compared to healthy people, with these differences being most pronounced in the order COVID-19 > RSV > FluA. Conversely, IL-6 and CRP levels were elevated across diseases, with IL-6 emerging as the most promising diagnostic biomarker, with areas under the curve (AUC) of the receiver operating characteristics plot higher than 0.85 and surpassing arachidonic acid and CRP. Moreover, IL-6 displayed notable efficacy in distinguishing between FluA patients who survived and those who did not (AUC = 0.80). These findings may provide useful tools for diagnosing and monitoring the severity of acute viral respiratory tract infections, ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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24. A red-fleshed apple rich in anthocyanins improves endothelial function, reduces inflammation, and modulates the immune system in hypercholesterolemic subjects: the AppleCOR study.

Author

Pedret, Anna, Companys, Judit, Calderón-Pérez, Lorena, Llauradó, Elisabet, Pla-Pagà, Laura, Salamanca, Patricia, Sandoval-Ramírez, Berner-Andree, Catalán, Úrsula, Fernández-Castillejo, Sara, Yuste, Silvia, Macià, Alba, Gutiérrez-Tordera, Laia, Bulló, Mónica, Camps, Jordi, Canela, Núria, Valls, Rosa Maria, Rubió-Piqué, Laura, Motilva, Maria José, and Solà, Rosa

Published
2024
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28. Hard wiring of normal tissue-specific chromosome-wide gene expression levels is an additional factor driving cancer type-specific aneuploidies

Author

Patkar, Sushant, Heselmeyer-Haddad, Kerstin, Auslander, Noam, Hirsch, Daniela, Camps, Jordi, Bronder, Daniel, Brown, Markus, Chen, Wei-Dong, Lokanga, Rachel, Wangsa, Darawalee, Wangsa, Danny, Hu, Yue, Lischka, Annette, Braun, Rüdiger, Emons, Georg, Ghadimi, B. Michael, Gaedcke, Jochen, Grade, Marian, Montagna, Cristina, Lazebnik, Yuri, Difilippantonio, Michael J., Habermann, Jens K., Auer, Gert, Ruppin, Eytan, and Ried, Thomas

Published
2021
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34. Retrospective Analysis of Clostridioides difficile Infection Rates and Outcomes in Hospitalized Patients during the COVID-19 Pandemic: A Unicenter Study in Reus, Spain.

Author

Iftimie, Simona, López-Azcona, Ana F., Corchero-Valverde, Mireia, Peralta-Vázquez, Antonio, López-Cordón, Laia Revuelta, García-Cervera, Carles, Fernández-Domínguez, Luís Manuel, Camps, Jordi, Joven, Jorge, and Castro, Antoni

Subjects
COVID-19, COVID-19 pandemic, CLOSTRIDIOIDES difficile, GASTROSCOPY, HOSPITAL patients, DELAYED diagnosis
Abstract

Background: Clostridioides difficile infections (CDI) vary in severity from mild diarrhea to life-threatening conditions like pseudomembranous colitis or toxic megacolon, often leading to sepsis and death. The COVID-19 pandemic prompted changes in healthcare practices, potentially affecting CDI incidence, though reported data are inconclusive. We studied factors influencing CDI incidence and outcomes at a university hospital throughout the COVID-19 pandemic years. Methods: We conducted a retrospective study on all adult hospitalized CDI cases from 1 January 2020 to 31 December 2022 in Hospital Universitari de Sant Joan in Reus. We collected demographic information, comorbid conditions, and concurrent infections. Results: While overall CDI and COVID-19 rates decreased in 2022, a notable increase in CDI infections was observed among oncological patients and those undergoing some aggressive treatments, such as colonoscopies or gastroscopies. The prevalence of comorbidities remained unmodified, and there were declines in prior gastrointestinal surgeries and proton pump inhibitor prescriptions. Factors associated with patient fatality or prolonged hospitalization included older age, cancer, chronic kidney disease, higher Charlson and McCabe indices, elevated C-reactive protein, and low albumin concentrations. Conclusions: Our study shows the evolving landscape of CDI during the COVID-19 pandemic and emphasizes the impact of delayed diagnoses and treatments exacerbated by telemedicine adoption. Identified risk factors for CDI-related mortality or prolonged hospital stays underscore the importance of targeted interventions in high-risk populations. [ABSTRACT FROM AUTHOR]

Published
2024
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38. 2837: Metabolic profiling of plasma and tissue in breast cancer patients: uncovering therapeutic response

Author

Jiménez-Franco, Andrea, Calderón, David, Jiménez-Aguilar, Juanma, Canela-Capdevila, Marta, García-Pablo, Raquel, Castañé, Helena, Araguas, Pablo, Malave, Bárbara, Acosta, Johana Cristina, Benavides, Rocío, Árquez, Miguel, Castaño, Fredy, Riu, Francesc, de la Flor, Miriam, Jordà, Coia, Melé, Mireia, Repkova, Jana, Amillano, Kepa, Camps, Jordi, Joven, Jorge, and Arenas, Meritxell

Published
2024
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42. Serum Arylesterase, Paraoxonase, and Lactonase Activities and Paraoxonase-1 Concentrations in Morbidly Obese Patients and Their Relationship with Non-Alcoholic Steatohepatitis.

Author

Castañé, Helena, Jiménez-Franco, Andrea, Martínez-Navidad, Cristian, Placed-Gallego, Cristina, Cambra-Cortés, Vicente, Perta, Adelina-Miruna, París, Marta, Castillo, Daniel del, Arenas, Meritxell, Camps, Jordi, and Joven, Jorge

Subjects
NON-alcoholic fatty liver disease, PARAOXONASE, OBESITY, HIGH density lipoproteins, TYPE 2 diabetes, HDL cholesterol
Abstract

Paraoxonase-1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). Reduced serum PON1 activity is found in diseases marked by oxidative stress and inflammation, but its role in obesity remains unclear. This study investigated PON1 activities and concentrations in morbidly obese individuals and explored the impacts of the genetic polymorphism PON1 rs662 and non-alcoholic fatty liver disease on enzymatic properties. We recruited 1349 morbidly obese patients undergoing bariatric surgery and 823 non-obese volunteers. PON1-related variables, including arylesterase, paraoxonase, and lactonase activities and PON1 concentrations, were examined. Our results showed that morbidly obese individuals exhibited higher PON1 concentrations but lower enzymatic activities than non-obese individuals. We observed inverse associations of arylesterase and paraoxonase activities with waist circumference (rho = −0.24, p < 0.001, and rho = −0.30, p < 0.001, respectively) and body mass index (rho = −0.15, p = 0.001, and rho = −0.23, p < 0.001), as well as direct associations of arylesterase, paraoxonase, and lactonase activities with HDL cholesterol (rho = 0.11, p = 0.005, rho = 0.20, p < 0.001, and rho = 0.20, p < 0.001). No significant differences were observed regarding metabolic syndrome, type 2 diabetes mellitus, hypertension, dyslipidemia, rs662 polymorphism allele frequencies, or the diagnosis of non-alcoholic steatohepatitis. Nevertheless, correlations were found between certain PON1-related variables, steatosis, and ballooning. In conclusion, changes in PON1-related variables in morbidly obese patients are dependent on the disease itself and HDL levels. The relationships between these variables and specific liver histological changes raise intriguing questions for consideration in future studies. [ABSTRACT FROM AUTHOR]

Published
2023
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49. Lymph Node Molecular Analysis with OSNA Enables the Identification of pT1 CRC Patients at Risk of Recurrence: A Multicentre Study.

Author

Saez de Gordoa, Karmele, Rodrigo-Calvo, Maria Teresa, Archilla, Ivan, Lopez-Prades, Sandra, Diaz, Alba, Tarragona, Jordi, Machado, Isidro, Ruiz Martín, Juan, Zaffalon, Diana, Daca-Alvarez, Maria, Pellisé, Maria, Camps, Jordi, and Cuatrecasas, Miriam

Subjects
RESEARCH, MOLECULAR diagnosis, SCIENTIFIC observation, LYMPH nodes, CANCER relapse, RETROSPECTIVE studies, COLORECTAL cancer, DESCRIPTIVE statistics, RESEARCH funding, LONGITUDINAL method, NUCLEIC acid amplification techniques
Abstract

Simple Summary: This study focuses on very-early-stage colorectal cancer (CRC), pT1, frequently diagnosed under the umbrella of CRC screening programs. There is a great deal of debate about how best to treat pT1 CRC to avoid the overtreatment or undertreatment of patients. The authors use the RT-PCR-based quantitative molecular assay OSNA (One-Step Nucleic Acid Amplification), which detects the presence and amount of metastatic tumour cells in the lymph nodes of pT1 CRC surgical specimens. Its positivity is related to high-risk clinicopathological features. This study gives insights into the application of OSNA in early-stage CRC and its usefulness in improving management decisions. Early-stage colorectal carcinoma (CRC)—pT1—is a therapeutic challenge and presents some histological features related to lymph node metastasis (LNM). A significant proportion of pT1 CRCs are treated surgically, resulting in a non-negligible surgical-associated mortality rate of 1.5–2%. Among these cases, approximately 6–16% exhibit LNM, but the impact on survival is unclear. Therefore, there is an unmet need to establish an objective and reliable lymph node (LN) staging method to optimise the therapeutic management of pT1 CRC patients and to avoid overtreating or undertreating them. In this multicentre study, 89 patients with pT1 CRC were included. All histological features associated with LNM were evaluated. LNs were assessed using two methods, One-Step Nucleic Acid Amplification (OSNA) and the conventional FFPE plus haematoxylin and eosin (H&E) staining. OSNA is an RT-PCR-based method for amplifying CK19 mRNA. Our aim was to assess the performance of OSNA and H&E in evaluating LNs to identify patients at risk of recurrence and to optimise their clinical management. We observed an 80.9% concordance in LN assessment using the two methods. In 9% of cases, LNs were found to be positive using H&E, and in 24.7% of cases, LNs were found to be positive using OSNA. The OSNA results are provided as the total tumour load (TTL), defined as the total tumour burden present in all the LNs of a surgical specimen. In CRC, a TTL ≥ 6000 CK19 m-RNA copies/µL is associated with poor prognosis. Three patients had TTL > 6000 copies/μL, which was associated with higher tumour budding. The discrepancies observed between the OSNA and H&E results were mostly attributed to tumour allocation bias. We concluded that LN assessment with OSNA enables the identification of pT1 CRC patients at some risk of recurrence and helps to optimise their clinical management. [ABSTRACT FROM AUTHOR]

Published
2023
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