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Multi-parametric profiling of renal cell, colorectal, and ovarian cancer identifies tumour-type-specific stroma phenotypes and a novel vascular biomarker

Corvigno, Sara; Frödin, Magnus; Wisman, G Bea A; Nijman, Hans W; Van der Zee, Ate GJ; Jirström, Karin LU ; Nodin, Björn LU ; Hrynchyk, Ina; Edler, David and Ragnhammar, Peter, et al. (2017) In The Journal of Pathology: Clinical Research 3(3). p.214-224
Abstract
Abstract A novel set of integrated procedures for quantification of fibroblast-rich stroma and vascular characteristics has recently been presented allowing discovery of novel perivascular and stromal biomarkers in colorectal, renal cell, and ovarian cancer. In the present study, data obtained through these procedures from clinically well-annotated collections of these three tumour types have been used to address two novel questions. First, data have been used to investigate if the three tumour types demonstrate significant differences regarding features such as vessel diameter, vessel density, and perivascular marker expression. Second, analyses of the cohorts have been used to explore the prognostic significance of a novel vascular... (More)
Abstract A novel set of integrated procedures for quantification of fibroblast-rich stroma and vascular characteristics has recently been presented allowing discovery of novel perivascular and stromal biomarkers in colorectal, renal cell, and ovarian cancer. In the present study, data obtained through these procedures from clinically well-annotated collections of these three tumour types have been used to address two novel questions. First, data have been used to investigate if the three tumour types demonstrate significant differences regarding features such as vessel diameter, vessel density, and perivascular marker expression. Second, analyses of the cohorts have been used to explore the prognostic significance of a novel vascular metric, ?vessel distance inter-quartile range (IQR)? that describes intra-case heterogeneity regarding vessel distribution. The comparisons between the three tumour types demonstrated a set of significant differences. Vessel density of renal cell cancer was statistically significantly higher than in colorectal and ovarian cancer. Vessel diameter was statistically significantly higher in ovarian cancer. Concerning perivascular status, colorectal cancer displayed significantly higher levels of perivascular PDGFR-? expression than the other two tumour types. Intra-case heterogeneity of perivascular PDGFR-? expression was also higher in colorectal cancer. Notably, these fibroblast-dominated stroma phenotypes matched previously described experimental tumour stroma characteristics, which have been linked to differential sensitivity to anti-VEGF drugs. High ?vessel distance IQR? was significantly associated with poor survival in both renal cell cancer and colorectal cancer. In renal cell cancer, this characteristic also acted as an independent prognostic marker according to multivariate analyses including standard clinico-pathological characteristics. Explorative subset analyses indicated particularly strong prognostic significance of ?vessel distance IQR? in T stage 4 of this cancer type. Together, these analyses identified tumour-type-specific vascular-stroma phenotypes of possible functional significance, and suggest ?vessel distance IQR? as a novel prognostic biomarker. (Less)
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published
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keywords
colorectal cancer, renal cell cancer, ovarian cancer, tumour microenvironment, vessels, pericytes, PDGFR-β, survival
in
The Journal of Pathology: Clinical Research
volume
3
issue
3
pages
11 pages
publisher
Wiley-Blackwell Publishing Ltd
ISSN
2056-4538
DOI
10.1002/cjp2.74
language
English
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yes
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f1b0320e-3a29-44ed-844e-15da0506e3f8
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2018-09-03 15:52:31
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2019-01-14 07:38:50
@article{f1b0320e-3a29-44ed-844e-15da0506e3f8,
  abstract     = {Abstract A novel set of integrated procedures for quantification of fibroblast-rich stroma and vascular characteristics has recently been presented allowing discovery of novel perivascular and stromal biomarkers in colorectal, renal cell, and ovarian cancer. In the present study, data obtained through these procedures from clinically well-annotated collections of these three tumour types have been used to address two novel questions. First, data have been used to investigate if the three tumour types demonstrate significant differences regarding features such as vessel diameter, vessel density, and perivascular marker expression. Second, analyses of the cohorts have been used to explore the prognostic significance of a novel vascular metric, ?vessel distance inter-quartile range (IQR)? that describes intra-case heterogeneity regarding vessel distribution. The comparisons between the three tumour types demonstrated a set of significant differences. Vessel density of renal cell cancer was statistically significantly higher than in colorectal and ovarian cancer. Vessel diameter was statistically significantly higher in ovarian cancer. Concerning perivascular status, colorectal cancer displayed significantly higher levels of perivascular PDGFR-? expression than the other two tumour types. Intra-case heterogeneity of perivascular PDGFR-? expression was also higher in colorectal cancer. Notably, these fibroblast-dominated stroma phenotypes matched previously described experimental tumour stroma characteristics, which have been linked to differential sensitivity to anti-VEGF drugs. High ?vessel distance IQR? was significantly associated with poor survival in both renal cell cancer and colorectal cancer. In renal cell cancer, this characteristic also acted as an independent prognostic marker according to multivariate analyses including standard clinico-pathological characteristics. Explorative subset analyses indicated particularly strong prognostic significance of ?vessel distance IQR? in T stage 4 of this cancer type. Together, these analyses identified tumour-type-specific vascular-stroma phenotypes of possible functional significance, and suggest ?vessel distance IQR? as a novel prognostic biomarker.},
  author       = {Corvigno, Sara and Frödin, Magnus and Wisman, G Bea A and Nijman, Hans W and Van der Zee, Ate GJ and Jirström, Karin and Nodin, Björn and Hrynchyk, Ina and Edler, David and Ragnhammar, Peter and Johansson, Martin and Dahlstrand, Hanna and Mezheyeuski, Artur and Östman, Arne},
  issn         = {2056-4538},
  keyword      = {colorectal cancer,renal cell cancer,ovarian cancer,tumour microenvironment,vessels,pericytes,PDGFR-β,survival},
  language     = {eng},
  month        = {06},
  number       = {3},
  pages        = {214--224},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {The Journal of Pathology: Clinical Research},
  title        = {Multi-parametric profiling of renal cell, colorectal, and ovarian cancer identifies tumour-type-specific stroma phenotypes and a novel vascular biomarker},
  url          = {http://dx.doi.org/10.1002/cjp2.74},
  volume       = {3},
  year         = {2017},
}