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Title: The prognostic impact of the tumour stroma fraction: A machine learning-based analysis in 16 human solid tumour types
Author: Micke, Patrick
Strell, Carina
Mattsson, Johanna
Martín Bernabé, Alfonso
Brunnström, Hans
Huvila, Jutta
Sund, Malin
Wärnberg, Fredrik
Ponten, Fredrik
Glimelius, Bengt
Hrynchyk, Ina
Mauchanski, Siarhei
Khelashvili, Salome
Garcia Vicién, Gemma
Molleví, David G.
Edqvist, Per-Henrik
O´Reilly, Aine
Corvigno, Sara
Dahlstrand, Hanna
Botling, Johan
Segersten, Ulrika
Krzyzanowska, Agnieszka
Bjartell, Anders
Elebro, Jacob
Heby, Margareta
Lundgren, Sebastian
Hedner, Charlotta
Borg, David
Brändstedt, Jenny
Sartor, Hanna
Malmström, Per-Uno
Johansson, Martin
Nodin, Björn
Backman, Max
Lindskog, Cecilia
Jirström, Karin
Mezheyeuski, Artur
Keywords: Tumors
Aprenentatge automàtic
Pronòstic mèdic
Machine learning
Issue Date: 1-Mar-2021
Publisher: Elsevier B. V.
Abstract: Background: The development of a reactive tumour stroma is a hallmark of tumour progression and pronounced tumour stroma is generally considered to be associated with clinical aggressiveness. The variability between tumour types regarding stroma fraction, and its prognosis associations, have not been systematically analysed. Methods: Using an objective machine-learning method we quantified the tumour stroma in 16 solid cancer types from 2732 patients, representing retrospective tissue collections of surgically resected primary tumours. Image analysis performed tissue segmentation into stromal and epithelial compartment based on pan-cytokeratin staining and autofluorescence patterns. Findings: The stroma fraction was highly variable within and across the tumour types, with kidney cancer showing the lowest and pancreato-biliary type periampullary cancer showing the highest stroma proportion (median 19% and 73% respectively). Adjusted Cox regression models revealed both positive (pancreato-biliary type periampullary cancer and oestrogen negative breast cancer, HR(95%CI)=0.56(0.34-0.92) and HR(95%CI)=0.41(0.17-0.98) respectively) and negative (intestinal type periampullary cancer, HR(95%CI)=3.59(1.49-8.62)) associations of the tumour stroma fraction with survival. Interpretation: Our study provides an objective quantification of the tumour stroma fraction across major types of solid cancer. Findings strongly argue against the commonly promoted view of a general associations between high stroma abundance and poor prognosis. The results also suggest that full exploitation of the prognostic potential of tumour stroma requires analyses that go beyond determination of stroma abundance. Funding: The Swedish Cancer Society, The Lions Cancer Foundation Uppsala, The Swedish Government Grant for Clinical Research, The Mrs Berta Kamprad Foundation, Sweden, Sellanders foundation, P.O.Zetterling Foundation, and The Sjöberg Foundation, Sweden.
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It is part of: EBioMedicine, 2021, vol. 65
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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