Biology subjects

Feliu, J.

Publications and source records attributed to Feliu, J..

3 recordsLinked to original sources

bioRxiv2019

Comprehensive characterization of the mutational landscape in localized anal squamous cell carcinoma

PurposeAnal squamous cell carcinoma (ASCC) is a rare neoplasm. Chemo-radiotherapy is the standard of care, with no therapeutic advances achieved over the past three decades. Thus, a deeper molecular characterization of this disease is still necessary.\n\nMethodsWe analyzed 46 paraffin-embedded tumor samples from patients diagnosed with primary ASCC by exome sequencing. A bioinformatics approach focused in the identification of high impact genetic variants, which may act as drivers of oncogenesis, was performed. The relation between genetics variant and prognosis was also studied.\n\nResultsThe list of high impact genetic variants was unique for each patient. However, the pathways in which these genes are involved are well-known hallmarks of cancer, such as angiogenesis or immune pathways. Additionally, we determined that genetic variants in BRCA2, ZNF750, FAM208B, ZNF599 and ZC3H13 genes are related with poor disease-free survival in ASCC.\n\nConclusionHigh impact genetic variants in ASCC affect pathways involved in cancer development, and may play a role in the etiology of the disease. Variants in BRCA2, ZNF750, FAM208B, ZNF599 and ZC3H13 genes seem to be related with prognosis in ASCC. Sequencing of ASCC clinical samples appears an encouraging tool for the molecular portrait of this disease.

cancer biology↗

bioRxiv2017

Probabilistic Graphical Models Relate Immune Status With Response To Neoadjuvant Chemo-Therapy In Breast Cancer

Breast cancer is the most frequent tumor in women and its incidence is increasing. Neoadjuvant chemotherapy has become standard of care as a complement to surgery in locally advanced or poor-prognosis early stage disease. The achievement of a complete response to neoadjuvant chemotherapy correlates with prognosis but it is not possible to predict who will obtain an excellent response. The molecular analysis of the tumor offers a unique opportunity to unveil predictive factors. In this work, gene expression profiling in 279 tumor samples from patients receiving neoadjuvant chemotherapy was performed and probabilistic graphical models were used. This approach enables addressing biological and clinical questions from a Systems Biology perspective, allowing to deal with large gene expression data and their interactions. Tumors presenting complete response to neoadjuvant chemotherapy had a higher activity of immune related functions compared to resistant tumors. Similarly, samples from complete responders presented higher expression of lymphocyte cell lineage markers, immune-activating and immune-suppressive markers, which may correlate with tumor infiltration by lymphocytes (TILs). These results suggest that the patients immune system plays a key role in tumor response to neoadjuvant treatment. However, future studies with larger cohorts are necessary to validate these hypotheses.

cancer biology↗

bioRxiv2017

Molecular characterization of breast cancer cell response to metabolic drugs

Metabolic reprogramming is a hallmark of cancer. We and other authors have previously shown that breast cancer subtypes present metabolism differences. In this study, breast cancer cell lines were treated with metformin and rapamycin. The response was heterogeneous across various breast cancer cells, leading to cell cycle disruption in specific conditions. The molecular effects of these treatments were characterized using sublethal doses, SNP genotyping and mass spectrometry-based proteomics. Protein expression was analyzed using probabilistic graphical models, showing that treatments elicit various responses in some biological processes, providing insights into cell responses to metabolism drugs. Moreover, a flux balance analysis approach using protein expression values was applied, showing that predicted growth rates were comparable with cell viability measurements and suggesting an increase in reactive oxygen species response enzymes due to metformin treatment. In addition, a method to assess flux differences in whole pathways was proposed. Our results show that these various approaches provide complementary information, which can be used to suggest hypotheses about the drugs mechanisms of action and the response to drugs that target metabolism.

systems biology↗