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Histopathology and levels of proteins in plasma associate with survival after colorectal cancer diagnosis
Authors
Famke Aeffner
Bjarni Agnar Agnarsson
+24 more
Kristín K. Alexíusdóttir
Kristbjorg Gunnarsdottir
Helga Sigrún Gunnarsdóttir
Daníel Fannar Guðbjartsson
Jón Gunnlaugur Jónasson
Erna María Jónsdóttir
Hildur Knutsdottir
Bjarney Sif Kristinsdóttir
Louise le Roux
Sigrún Helga Lund
Droplaug N. Magnusdottir
Olafur T. Magnusson
Magnús Ingvi Magnússon
Gudmundur L. Norddahl
Sigurgeir Olafsson
Thorunn Rafnar
Hjaltey Runarsdottir
Jona Saemundsdottir
Kári Stefánsson
Emilia Söebech
Þórður Tryggvason
J. E.Vivienne Watson
Magnús Örn Úlfarsson
Unnur Þorsteinsdóttir
Publication date
19 October 2023
Publisher
Doi
Cite
Abstract
Funding Information: The authors thank the subjects who have donated their time and their samples that were used in this research. Publisher Copyright: © 2023, The Author(s).Background: The TNM system is used to assess prognosis after colorectal cancer (CRC) diagnosis. Other prognostic factors reported include histopathological assessments of the tumour, tumour mutations and proteins in the blood. As some of these factors are strongly correlated, it is important to evaluate the independent effects they may have on survival. Methods: Tumour samples from 2162 CRC patients were visually assessed for amount of tumour stroma, severity of lymphocytic infiltrate at the tumour margins and the presence of lymphoid follicles. Somatic mutations in the tumour were assessed for 2134 individuals. Pre-surgical levels of 4963 plasma proteins were measured in 128 individuals. The associations between these features and prognosis were inspected by a Cox Proportional Hazards Model (CPH). Results: Levels of stroma, lymphocytic infiltration and presence of lymphoid follicles all associate with prognosis, along with high tumour mutation burden, high microsatellite instability and TP53 and BRAF mutations. The somatic mutations are correlated with the histopathology and none of the somatic mutations associate with survival in a multivariate analysis. Amount of stroma and lymphocytic infiltration associate with local invasion of tumours. Elevated levels of two plasma proteins, CA-125 and PPP1R1A, associate with a worse prognosis. Conclusions: Tumour stroma and lymphocytic infiltration variables are strongly associated with prognosis of CRC and capture the prognostic effects of tumour mutation status. CA-125 and PPP1R1A may be useful prognostic biomarkers in CRC.Peer reviewe
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Last time updated on 25/10/2023