title: Widespread parainflammation in human cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Institute for Computational Health Sciences, University of California, San Francisco, California, 94158, USA.
authors.forename: Dvir
authors.initials: D
authors.lastname: Aran
authors.affiliation: The Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.
authors.forename: Audrey
authors.initials: A
authors.lastname: Lasry
authors.affiliation: The Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.
authors.forename: Adar
authors.initials: A
authors.lastname: Zinger
authors.affiliation: The Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Biton
authors.affiliation: The Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Pikarsky
authors.affiliation: Developmental Biology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Asaf
authors.initials: A
authors.lastname: Hellman
authors.affiliation: Institute for Computational Health Sciences, University of California, San Francisco, California, 94158, USA. atul.butte@uscf.edu.
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.affiliation: The Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel. yinonb@ekmd.huji.ac.il.
authors.forename: Yinon
authors.initials: Y
authors.lastname: Ben-Neriah
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D063646:Carcinogenesis / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D051379:Mice; D009154:Mutation; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Cancer prevention; Genomics; Inflammation; NSAID treatment; Parainflammation; p53 mutations