Intra-tumour signalling entropy determines clinical outcome in breast and lung cancer

PLoS Computational Biology
Christopher R S BanerjiAndrew E Teschendorff

Abstract

The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample's genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, ...Continue Reading

References

Oct 1, 1976·Science·P C Nowell
Nov 2, 2001·Nature·T ReyaI L Weissman
Feb 2, 2002·Nature·Laura J van 't VeerStephen H Friend
Dec 20, 2002·The New England Journal of Medicine·Marc J van de VijverRené Bernards
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Al-HajjMichael F Clarke
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Celina G KleerArul M Chinnaiyan
Aug 17, 2004·Bioinformatics·Liat Ein-DorEytan Domany
Sep 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Lance D MillerJonas Bergh
Feb 16, 2006·Journal of the National Cancer Institute·Christos SotiriouMauro Delorenzi
Mar 28, 2006·Nature Genetics·Carlo C MaleyBrian J Reid
Apr 3, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sherene LoiChristos Sotiriou
Jun 5, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christine DesmedtUNKNOWN TRANSBIG Consortium
Sep 14, 2007·Nature Reviews. Cancer·John Stingl, Carlos Caldas
Jul 3, 2008·Cancer Research·Marcus SchmidtMathias Gehrmann
Jul 22, 2008·Nature Medicine·UNKNOWN Director's Challenge Consortium for the Molecular Classification of Lung AdenocarcinomaDavid G Beer
Feb 11, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joel S ParkerPhilip S Bernard
Dec 1, 2007·Molecular Oncology·Fatima CardosoUNKNOWN TRANSBIG Consortium
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Chad J CreightonJenny C Chang
Sep 10, 2009·Cell·Mark ShackletonSean J Morrison
Oct 8, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Khaled A HassanDavid G Beer
Dec 17, 2009·The Lancet Oncology·Fabrice Andre, Suzette Delaloge
Mar 18, 2010·Journal of the National Cancer Institute·Jyothi Subramanian, Richard Simon
Jun 10, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fumi Takahashi-Yanaga, Michael Kahn
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Joseph H TaubeSendurai A Mani
Sep 4, 2010·Breast Cancer Research : BCR·Aleix PratCharles M Perou
Oct 6, 2010·Journal of the National Cancer Institute·Paul C BoutrosIgor Jurisica
Dec 22, 2010·Bioinformatics·Wessel N van Wieringen, Aad W van der Vaart
May 7, 2011·Bioinformatics·Arthur LiberzonJill P Mesirov
Oct 27, 2011·PLoS Computational Biology·David VenetVincent Detours
Mar 6, 2012·Lancet·Yang Xie, John D Minna
Mar 9, 2012·The New England Journal of Medicine·Marco GerlingerCharles Swanton
Sep 13, 2012·Nature Communications·Alejandra BrunaCarlos Caldas
Oct 4, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Johan BotlingPatrick Micke
Oct 27, 2012·Science Translational Medicine·Yinyin YuanFlorian Markowetz

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Citations

Sep 1, 2015·Translational Research : the Journal of Laboratory and Clinical Medicine·Jeremy T-H ChangR Stephanie Huang
Nov 25, 2016·Scientific Reports·Youngjune ParkSun Kim
Jun 2, 2017·Nature Communications·Andrew E Teschendorff, Tariq Enver
Dec 20, 2017·Nature Communications·Christopher R S BanerjiPeter S Zammit
Sep 18, 2015·Bulletin of Mathematical Biology·Wessel N van Wieringen, Aad W van der Vaart
Dec 19, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Simone EckerDirk S Paul
Feb 22, 2018·Oncogene·Santiago Ramon Y CajalNahum Sonenberg
Aug 25, 2016·Genome Medicine·Jordi Serra-MusachMiquel Àngel Pujana
Apr 23, 2020·Frontiers in Genetics·Alessandra Jordano ConforteFabrício Alves Barbosa da Silva
Aug 9, 2020·Frontiers in Bioengineering and Biotechnology·Chongyin HanFei Ling
Nov 7, 2019·Frontiers in Genetics·Alessandra J ConforteNicolas Carels
Feb 28, 2019·Cancer Research·Grace G BushnellLonnie D Shea
Jun 8, 2021·Journal of Molecular Cell Biology·Li FengRong Zeng

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Datasets Mentioned

BETA
GSE2361

Methods Mentioned

BETA
biopsies
RNA-seq

Software Mentioned

METABRIC
scripts
R
OncotypeDX
MammaPrint
MEATBRIC

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