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Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer

Author

  • Artur Mezheyeuski
  • Maja Bradic Lindh
  • Tormod Kyrre Guren
  • Anca Dragomir
  • Per Pfeiffer
  • Elin H Kure
  • Tone Ikdahl
  • Eva Skovlund
  • Sara Corvigno
  • Carina Strell
  • Kristian Pietras
  • Fredrik Ponten
  • Jan Mulder
  • Camilla Qvortrup
  • Anna Portyanko
  • Kjell Magne Tveit
  • Bengt Glimelius
  • Halfdan Sorbye
  • Arne Östman
Show all

Summary, in English

Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown.Here we report a novel method for digital quantitative analyses of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC).Initial analyses identified marker-defined subsets of PC, including cells expressing PDGFR-β or α-SMA or both markers. PC subsets were largely independently expressed in a manner unrelated to vessel density and size. Association studies implied specific oncogenic mutations in malignant cells as determinants of PC status. Semi-quantitative and digital-image-analyses-based scoring of the NORDIC-VII cohort identified significant associations between low expression of perivascular PDGFR-α and -β and shorter overall survival. Analyses of the SPCRC cohort confirmed these findings. Perivascular PDGFR-α and -β remained independent factors for survival in multivariate analyses.Overall, our study identified host vasculature and oncogenic status as determinants of tumor perivascular features. Perivascular PDGFR-α and -β were identified as novel independent markers predicting survival in mCRC. The novel methodology should be suitable for similar analyses in other tumor collections.

Department/s

  • Division of Translational Cancer Research
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

Publishing year

2016-07-05

Language

English

Pages

41948-41958

Publication/Series

Oncotarget

Volume

7

Issue

27

Document type

Journal article

Publisher

Impact Journals

Topic

  • Cancer and Oncology

Keywords

  • Actins/metabolism
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Biomarkers, Tumor/metabolism
  • Cohort Studies
  • Colorectal Neoplasms/blood supply
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Pericytes/metabolism
  • Receptor, Platelet-Derived Growth Factor alpha/metabolism
  • Receptor, Platelet-Derived Growth Factor beta/metabolism
  • Young Adult

Status

Published

ISBN/ISSN/Other

  • ISSN: 1949-2553