| 1. |
- Brady, Lauren, et al.
(författare)
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Correlation of integrated ERG/PTEN assessment with biochemical recurrence in prostate cancer
- 2021
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Ingår i: Cancer Treatment and Research Communications. - : Elsevier. - 2468-2942. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Prostate cancer is a heterogeneous disease, with a complex molecular landscape that evolves throughout disease progression. Common alterations in genes such as ERG and PTEN have been attributed to worse prognosis. This study aimed to further examine the clinical relevance of PTEN and ERG expression in a cohort of patients with prostate cancer post radical prostatectomy.METHODS: Tissue microarrays were constructed from 132 patients with prostate cancer from the Irish Prostate Cancer Research Consortium and University Hospital of Orebro, Sweden. Patients were divided into three groups - Group 1: biochemical recurrence, Group 2: no biochemical recurrence and Group 3: immediate progression after surgery. PTEN and ERG immunohistochemical analysis was performed and the association between expression levels and clinical parameters were compared.RESULTS: Pathological stage pT3 tumours were more common at borderline significantly higher levels amongst patients who biochemically recurred when compared to patients who did not recur after radical prostatectomy (p = 0.05). ERG and PTEN expression levels were compared separately and concurrently across all three patient groups. Lack of ERG expression was strongly associated with immediate progression after surgery (p = 0.029). Loss of/low PTEN trended towards an association with immediate progression, however this was not statistically significant (p = 0.066).CONCLUSION: In this study, negative ERG expression was strongly associated with immediate biochemical progression after radical prostatectomy. Moreover, a trend towards a relationship between aberrant PTEN expression and progression was observed. Additional studies with long-term follow up data may provide further clinical insight into the genomic heterogeneity in this population.
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| 2. |
- Lawler, Mark, et al.
(författare)
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European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.
- 2023
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Ingår i: The Lancet. Oncology. - 1474-5488 .- 1470-2045. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average survival for all European cancer patients by 2035.
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| 3. |
- Loughman, Tony, et al.
(författare)
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Analytical Validation of a Novel 6-Gene Signature for Prediction of Distant Recurrence in Estrogen Receptor-Positive, HER2-Negative, Early-Stage Breast Cancer
- 2022
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 68:6, s. 837-847
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOncoMasTR is a recently developed multigene prognostic test for early-stage breast cancer. The test has been developed in a kit-based format for decentralized deployment in molecular pathology laboratories. The analytical performance characteristics of the OncoMasTR test are described in this study.MethodsExpression levels of 6 genes were measured by 1-step reverse transcription-quantitative PCR on RNA samples prepared from formalin-fixed, paraffin-embedded (FFPE) breast tumor specimens. Assay precision, reproducibility, input range, and interference were determined using FFPE-derived RNA samples representative of low and high prognostic risk scores. A pooled RNA sample derived from 6 FFPE breast tumor specimens was used to establish the linear range, limit of detection, and amplification efficiency of the individual gene expression assays.ResultsThe overall precision of the OncoMasTR test was high with an SD of 0.16, which represents less than 2% of the 10-unit risk score range. Test results were reproducible across 4 testing sites, with correlation coefficients of 0.94 to 0.96 for the continuous risk score and concordance of 86% to 96% in low-/high-risk sample classification. Consistent risk scores were obtained across a > 100-fold RNA input range. Individual gene expression assays were linear up to quantification cycle values of 36.0 to 36.9, with amplification efficiencies of 80% to 102%. Test results were not influenced by agents used during RNA isolation, by low levels of copurified genomic DNA, or by moderate levels of copurified adjacent nontumor tissue.ConclusionThe OncoMasTR prognostic test displays robust analytical performance that is suitable for deployment by local pathology laboratories for decentralized use.
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| 4. |
- Wedman, Jonathan, 1983-
(författare)
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Theory and validity evidence for a large-scale test for selection to higher education
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Validity is a crucial part of all forms of measurement, and especially in instruments that are high-stakes to the test takers. The aim of this thesis was to examine theory and validity evidence for a recently revised large-scale instrument used for selection to higher education in Sweden, the Swedish Scholastic Assessment Test (SweSAT), as well as identify threats to its validity. Previous versions of the SweSAT have been intensely studied but when it was revised in 2011, further research was needed to strengthen the validity arguments for the test. The validity approach suggested in the most recent version of the Standards for education and psychological testing, in which the theoretical basis and five sources of validity evidence are the key aspects of validity, was adopted in this thesis.The four studies that are presented in this thesis focus on different aspects of the SweSAT, including theory, score reporting, item functioning and linking of test forms. These studies examine validity evidence from four of the five sources of validity: evidence based on test content, response processes, internal structure and consequences of testing.The results from the thesis as a whole show that there is validity evidence that supports some of the validity arguments for the intended interpretations and uses of SweSAT scores, and that there are potential threats to validity that require further attention. Empirical evidence supports the two-dimensional structure of the construct scholastic proficiency, but the construct requires a more thorough definition in order to better examine validity evidence based on content and consequences for test takers. Section scores provide more information about test takers' strengths and weaknesses than what is already provided by the total score and can therefore be reported, but subtest scores do not provide additional information and should not be reported. All four quantitative subtests, as well as the Swedish reading comprehension subtest, are essentially free of differential item functioning (DIF) but there is moderate DIF that could be bias in two of the four verbal subtests. Finally, the equating procedure, although it appears to be appropriate, needs to be examined further in order to determine whether it is the best practice available or not for the SweSAT.Some of the results in this thesis are specific to the SweSAT because only SweSAT data was used but the design of the studies and the methods that were applied serve as practical examples of validating a test and are therefore likely useful to different populations of people involved in test development, test use and psychometric research.Suggestions for further research include: (1) a study to create a more clear and elaborate definition of the construct, scholastic proficiency; (2) a large and empirically focused study of subscore value in the SweSAT using repeat test takers and applying Haberman’s method along with recently proposed effect size measures; (3) a cross-validation DIF-study using more recently administered test forms; (4) a study that examines the causes for the recurring score differences between women and men on the SweSAT; and (5) a study that re-examines the best practice for equating the current version of the SweSAT, using simulated data in addition to empirical data.
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