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Correlations between immune response and vascularization qRT-PCR gene expression clusters in squamous cervical cancer

Overview of attention for article published in Molecular Cancer, March 2015
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Title
Correlations between immune response and vascularization qRT-PCR gene expression clusters in squamous cervical cancer
Published in
Molecular Cancer, March 2015
DOI 10.1186/s12943-015-0350-0
Pubmed ID
Authors

Simone Punt, Jeanine J Houwing-Duistermaat, Iris A Schulkens, Victor L Thijssen, Elisabeth M Osse, Cornelis D de Kroon, Arjan W Griffioen, Gert Jan Fleuren, Arko Gorter, Ekaterina S Jordanova

Abstract

The tumour microenvironment comprises a network of immune response and vascularization factors. From this network, we identified immunological and vascularization gene expression clusters and the correlations between the clusters. We subsequently determined which factors were correlated with patient survival in cervical carcinoma. The expression of 42 genes was investigated in 52 fresh frozen squamous cervical cancer samples by qRT-PCR. Weighted gene co-expression network analysis and mixed-model analyses were performed to identify gene expression clusters. Correlations and survival analyses were further studied at expression cluster and single gene level. We identified four immune response clusters: 'T cells' (CD3E/CD8A/TBX21/IFNG/FOXP3/IDO1), 'Macrophages' (CD4/CD14/CD163), 'Th2' (IL4/IL5/IL13/IL12) and 'Inflammation' (IL6/IL1B/IL8/IL23/IL10/ARG1) and two vascularization clusters: 'Angiogenesis' (VEGFA/FLT1/ANGPT2/ PGF/ICAM1) and 'Vessel maturation' (PECAM1/VCAM1/ANGPT1/SELE/KDR/LGALS9). The 'T cells' module was correlated with all modules except for 'Inflammation', while 'Inflammation' was most significantly correlated with 'Angiogenesis' (p < 0.001). High expression of the 'T cells' cluster was correlated with earlier TNM stage (p = 0.007). High CD3E expression was correlated with improved disease-specific survival (p = 0.022), while high VEGFA expression was correlated with poor disease-specific survival (p = 0.032). Independent predictors of poor disease-specific survival were IL6 (hazard ratio = 2.3, p = 0.011) and a high IL6/IL17 ratio combined with low IL5 expression (hazard ratio = 4.2, p = 0.010). 'Inflammation' marker IL6, especially in combination with low levels of IL5 and IL17, was correlated with poor survival. This suggests that IL6 promotes tumour growth, which may be suppressed by a Th17 and Th2 response. Measuring IL6, IL5 and IL17 expression may improve the accuracy of predicting prognosis in cervical cancer.

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Geographical breakdown

Country Count As %
United Kingdom 1 3%
Unknown 39 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 20%
Student > Master 6 15%
Researcher 5 13%
Student > Bachelor 4 10%
Professor 3 8%
Other 8 20%
Unknown 6 15%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 25%
Medicine and Dentistry 9 23%
Agricultural and Biological Sciences 5 13%
Immunology and Microbiology 4 10%
Physics and Astronomy 2 5%
Other 4 10%
Unknown 6 15%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 January 2016.
All research outputs
#14,718,998
of 23,577,654 outputs
Outputs from Molecular Cancer
#944
of 1,782 outputs
Outputs of similar age
#141,937
of 266,121 outputs
Outputs of similar age from Molecular Cancer
#24
of 56 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,782 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one is in the 43rd percentile – i.e., 43% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 266,121 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 56 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.