ESS - DM - Bioestatística e Bioinformática Aplicadas à Saúde
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Browsing ESS - DM - Bioestatística e Bioinformática Aplicadas à Saúde by advisor "Antunes, Luís"
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- Comparative study of adjustement methods for confounding variablesPublication . Silva, Inês Fortuna Alves da; Antunes, Luís; Faria, Brígida MónicaObservational studies provide relevant evidence; however, they have an inherent lack of balance of baseline variables distribution between the study groups, making it difficult to understand the real treatment effect. There are many methods to balance the confounders. Traditional covariate adjustment is the most used however, currently, it is also common to apply techniques based on propensity score (PS). One of them is Inverse Probability of Treatment Weighting (IPTW). The application of IPTW involves comparing two groups of samples weighed by inverse probability of treatment. The main advantage of using IPTW, compared to other PS techniques, is to allow all patient data to be preserved, and compared to classical adjustment methods, it allows balancing and evaluating this balance of confounders before assessing the outcome. In this study, the effect of two neoadjuvant treatments for HER2-positive breast cancer was analysed. The treatments differed in four additional cycles of pertuzumab. Two methods of balancing the distribution of variables were applied, the IPTW and the traditional regression adjustment methods. The results after the application of both mentioned techniques permitted to conclude that the therapy with double-block anti-HER2 seems more favourable. Besides, this treatment enabled a greater number of patients with pathologic complete response (pCR). It also allowed a reduction in the number of radical mastectomies. Although there were statistically significant differences in the type of surgert between the study groups, the difference in pCR was not significant (p > 0.05). This work had some limitations, such as the low number of patients with certain characteristics, among other factors, which conditioned a clear perception of the results. In this sense, it will be useful to expand this study to include more patients with heterogeneous features, allowing to get more robust conclusions.
- Estudo epidemiológico da incidência e sobrevivência do cancro em pacientes da Região Norte de Portugal e IPO-PortoPublication . Silva, Soraia Alexandra Cardoso da; Antunes, Luís; Oliveira, AlexandraO cancro é um problema de saúde pública mundial. As estatísticas, tanto de incidência como de sobrevivência, são uma ferramenta importante para monitorizar os avanços do controlo do cancro e chamar a atenção para as áreas onde existe necessidade de intervenção. O objetivo deste trabalho foi auxiliar o Registo Oncológico Regional do Norte (RORENO), no sentido de criar as publicações de sobrevivência e incidência com dados dos doentes oncológicos da região norte de Portugal e dos doentes do IPO, pelas quais esta instituição é responsável. Assim sendo, para as publicações de incidência foi utilizado o software Excel tanto para os cálculos como para a criação de tabelas e gráficos necessários. Por sua vez, para o caso das publicações referentes à sobrevivência da doença oncológica, foi utilizado o software R para a análise das sobrevivências e o LATEX para a criação do formato final das publicações. As publicações de incidência, como o próprio nome indica, apresentam o número de casos novos de cancro para o ano em estudo, tanto para os doentes registados na região Norte como também para doentes diagnosticados apenas no IPO-Porto. Por outro lado, para cada uma das publicações de sobrevivência, são apresentados resultados da sobrevivência observada e da sobrevivência “net”. Para a sobrevivência observada foi utilizado o estimador de Kaplan-Meier e para a sobrevivência “net” um estimador recente, designado por Pohar-Perme. Também são apresentadas sobrevivências estratificadas por algumas variáveis: sexo, grupo etário, distrito de residência, extensão da doença e tipo histológico da doença. Além disto, foram calculadas as sobrevivências padronizadas para certos tipos de cancro e realizadas comparações entre curvas de sobrevivência e biénios, utilizando um teste do tipo log-rank para a sobrevivência “net”. Desse modo, no final do estágio foram obtidas duas publicações de incidência, uma direcionada ao estudo de incidência de cancro no Norte de Portugal, no ano de 2012, e outra direcionada à incidência de cancro no IPO do Porto, no ano de 2017. Além destas, foram também obtidas duas publicações relativas ao estudo da sobrevivência da doença oncológica, uma a para região Norte de Portugal e outra para o IPO-Porto, ambas no biénio 2011-2012.
- In silico dessection of the immunomodulatory effects of cholesterol on colorectal cancerPublication . Machado, Ana Luísa Marinho da Cunha; Fernandes, Verónica; Velho, Sérgia; Antunes, LuísCholesterol plays a pivotal role in the progression of tumors, serving as a crucial component for cell membrane formation and the generation of specific proteins and enzymes that stimulate the growth and dissemination of tumor cells. Additionally, cholesterol levels within the tumor microenvironment exert influence over immune responses by hindering the activity of vital components like T-cells and NK-cells, which are indispensable for effective anti-cancer immunity. The primary objective of this research is to investigate whether it is possible to categorize colon cancer tumors based on disparities in cholesterol-related characteristics and whether these groupings correlate with distinct immune profiles. The Cancer Genome Atlas (TCGA) project is an open-access catalog aiming to comprehensively understand the genomic alterations responsible for various cancer types, by encompassing a vast array of molecular data from thousands of patient samples. One of the pivotal advantages of utilizing TCGA data lies in its sheer scale and diversity. By integrating genomic, transcriptomic, proteomic, and clinical data from a multitude of patients, researchers can identify patterns, mutations, and biomarkers associated with specific cancers. Taking advantage of this catalog, we selected TCGA RNA-seq dataset from patients with colorectal cancer (480 tumor colon samples and 167 tumor rectum samples). Firstly, we used the Gene Set Enrichment Analysis (GSEA) tool, a powerful tool employed in bioinformatics and computational biology, to determine the sets of genes and pathways that showed statistically significance. Upon comparing these samples with their corresponding normal adjacent tissues, notable disparities in lipid metabolism were discerned. While cholesterol-related pathways did not rank as the top differentially regulated pathways, we exclusively observed an upregulation of lipid-related pathways in normal adjacent tissue in comparison to tumor tissue within the colon samples. Subsequently, we conducted in-depth analyses to determine whether colon tumors can be stratified based on differences in cholesterol metabolism and whether these variations correlate with disparities in the tumor microenvironment.By using the ssGSEA scores of the pathways related to cholesterol metabolism we employed the k-means method to cluster the samples. Remarkably, colon tumor samples naturally segregated into two distinct groups: one characterized by low expression of cholesterol-related genes and the other exhibiting increased expression. Notably, these groupings exhibited disparities in colon sample staging and the prevalence of molecular subtypes within each category. The group displaying enhanced cholesterol metabolism showcased reduced prolifiv eration, underscoring the significance of tumor microenvironment remodeling. Among the top enriched pathways, were pathways associated with modified antigen presentation, cytotoxic immune responses, and remodeling of the extracellular matrix. These observations were consistent with increased infiltration of immune cells driven by the activation of cholesterol metabolism. However, despite the higher quantity of these immune cells, their activation levels were lower in tumors characterized by upregulated cholesterol metabolism. Comparison of signaling pathways between these groups revealed significant differences in pathways linked to tumor malignancy. In summary, these findings underscore the role of cholesterol metabolism alterations in driving substantial adaptations within the tumor microenvironment. Stratifying colon tumors based on cholesterol metabolism presents a promising avenue, potentially benefiting patients through immunotherapy and cholesterol modulation as adjuvant therapy.