1. Towards biomarkers for outcomes after pancreatic ductal adenocarcinoma and ischaemic stroke, with focus on (co)-morbidity and ageing/cellular senescence (SASKit): protocol for a prospective cohort study.
- Author
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Henze L, Walter U, Murua Escobar H, Junghanss C, Jaster R, Köhling R, Lange F, Salehzadeh-Yazdi A, Wolkenhauer O, Hamed M, Barrantes I, Palmer D, Möller S, Kowald A, Heussen N, and Fuellen G
- Subjects
- Aging, COVID-19, Cellular Senescence, Cohort Studies, Comorbidity, Female, Germany epidemiology, Humans, Male, Prospective Studies, Quality of Life, SARS-CoV-2, Adenocarcinoma epidemiology, Brain Ischemia, Ischemic Stroke, Pancreatic Neoplasms epidemiology, Stroke epidemiology
- Abstract
Introduction: Ageing-related processes such as cellular senescence are believed to underlie the accumulation of diseases in time, causing (co)morbidity, including cancer, thromboembolism and stroke. Interfering with these processes may delay, stop or reverse morbidity. The aim of this study is to investigate the link between (co)morbidity and ageing by exploring biomarkers and molecular mechanisms of disease-triggered deterioration in patients with pancreatic ductal adenocarcinoma (PDAC) and (thromboembolic) ischaemic stroke (IS)., Methods and Analysis: We will recruit 50 patients with PDAC, 50 patients with (thromboembolic) IS and 50 controls at Rostock University Medical Center, Germany. We will gather routine blood data, clinical performance measurements and patient-reported outcomes at up to seven points in time, alongside in-depth transcriptomics and proteomics at two of the early time points. Aiming for clinically relevant biomarkers, the primary outcome is a composite of probable sarcopenia, clinical performance (described by ECOG Performance Status for patients with PDAC and the Modified Rankin Scale for patients with stroke) and quality of life. Further outcomes cover other aspects of morbidity such as cognitive decline and of comorbidity such as vascular or cancerous events. The data analysis is comprehensive in that it includes biostatistics and machine learning, both following standard role models and additional explorative approaches. Prognostic and predictive biomarkers for interventions addressing senescence may become available if the biomarkers that we find are specifically related to ageing/cellular senescence. Similarly, diagnostic biomarkers will be explored. Our findings will require validation in independent studies, and our dataset shall be useful to validate the findings of other studies. In some of the explorative analyses, we shall include insights from systems biology modelling as well as insights from preclinical animal models. We anticipate that our detailed study protocol and data analysis plan may also guide other biomarker exploration trials., Ethics and Dissemination: The study was approved by the local ethics committee (Ethikkommission an der Medizinischen Fakultät der Universität Rostock, A2019-0174), registered at the German Clinical Trials Register (DRKS00021184), and results will be published following standard guidelines., Competing Interests: Competing interests: UW reports personal fees from Ipsen Pharma, grants and personal fees from Merz Pharma, personal fees from Allergan, personal fees from Bristol-Myers Squibb, personal fees from Daiichi Sankyo, personal fees from Bayer Vital, personal fees from Boehringer Ingelheim, personal fees from Pfizer, personal fees from Thieme, and personal fees from Elsevier Press, all outside the submitted work. The other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2020
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