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

Mezheyeuski, Artur ; Bradic Lindh, Maja ; Guren, Tormod Kyrre ; Dragomir, Anca ; Pfeiffer, Per ; Kure, Elin H ; Ikdahl, Tone ; Skovlund, Eva ; Corvigno, Sara and Strell, Carina , et al. (2016) In Oncotarget 7(27). p.41948-41958
Abstract

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.... (More)

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.

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publication status
published
subject
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
in
Oncotarget
volume
7
issue
27
pages
11 pages
publisher
Impact Journals
external identifiers
  • pmid:27248825
  • scopus:85009706499
ISSN
1949-2553
DOI
10.18632/oncotarget.9632
language
English
LU publication?
yes
id
b5f53d31-f068-4379-86e0-dbd23651a1a8
date added to LUP
2019-06-19 21:24:39
date last changed
2025-01-09 15:24:48
@article{b5f53d31-f068-4379-86e0-dbd23651a1a8,
  abstract     = {{<p>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.</p>}},
  author       = {{Mezheyeuski, Artur and Bradic Lindh, Maja and Guren, Tormod Kyrre and Dragomir, Anca and Pfeiffer, Per and Kure, Elin H and Ikdahl, Tone and Skovlund, Eva and Corvigno, Sara and Strell, Carina and Pietras, Kristian and Ponten, Fredrik and Mulder, Jan and Qvortrup, Camilla and Portyanko, Anna and Tveit, Kjell Magne and Glimelius, Bengt and Sorbye, Halfdan and Östman, Arne}},
  issn         = {{1949-2553}},
  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}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{27}},
  pages        = {{41948--41958}},
  publisher    = {{Impact Journals}},
  series       = {{Oncotarget}},
  title        = {{Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer}},
  url          = {{http://dx.doi.org/10.18632/oncotarget.9632}},
  doi          = {{10.18632/oncotarget.9632}},
  volume       = {{7}},
  year         = {{2016}},
}