Widespread parainflammation in human cancer

Dvir Aran, Audrey Lasry, Adar Zinger, Moshe Biton, Eli Pikarsky, Asaf Hellman, Atul J. Butte*, Yinon Ben-Neriah

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Background: Chronic inflammation has been recognized as one of the hallmarks of cancer. We recently showed that parainflammation, a unique variant of inflammation between homeostasis and chronic inflammation, strongly promotes mouse gut tumorigenesis upon p53 loss. Here we explore the prevalence of parainflammation in human cancer and determine its relationship to certain molecular and clinical parameters affecting treatment and prognosis. Results: We generated a transcriptome signature to identify parainflammation in many primary human tumors and carcinoma cell lines as distinct from their normal tissue counterparts and the tumor microenvironment and show that parainflammation-positive tumors are enriched for p53 mutations and associated with poor prognosis. Non-steroidal anti-inflammatory drug (NSAID) treatment suppresses parainflammation in both murine and human cancers, possibly explaining a protective effect of NSAIDs against cancer. Conclusions: We conclude that parainflammation, a low-grade form of inflammation, is widely prevalent in human cancer, particularly in cancer types commonly harboring p53 mutations. Our data suggest that parainflammation may be a driver for p53 mutagenesis and a guide for cancer prevention by NSAID treatment.

Original languageAmerican English
Article number145
JournalGenome Biology
Volume17
Issue number1
DOIs
StatePublished - 8 Jul 2016

Bibliographical note

Funding Information:
This work was supported by the Gruss Lipper Postdoctoral Fellowship to D.A., grants from the Israel Science Foundation (ISF)—Centers of Excellence and the European Research Council within the FP-7 to YB-N (294390 PICHO) and EP (281738 LIVERMICROENV), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF), the I-CORE program of ISF (grant number 41/11) and the Israel Cancer Research fund to Y.B.N., and Israel Science Foundation grant number 1162/12, I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation grant number 41/11, and the Rosetrees Trust grant to A.H and the National Cancer Institute of the National Institutes of Health U24 CA195858 to A.J.B.

Publisher Copyright:
© 2016 The Author(s).

Keywords

  • Cancer prevention
  • Genomics
  • Inflammation
  • NSAID treatment
  • P53 mutations
  • Parainflammation

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