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Immune Response Gene Expression in Colorectal Cancer Carries Distinct Prognostic Implications According to Tissue, Stage and Site: A Prospective Retrospective Translational Study in the Context of a…

Overview of attention for article published in PLOS ONE, May 2015
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Title
Immune Response Gene Expression in Colorectal Cancer Carries Distinct Prognostic Implications According to Tissue, Stage and Site: A Prospective Retrospective Translational Study in the Context of a Hellenic Cooperative Oncology Group Randomised Trial
Published in
PLOS ONE, May 2015
DOI 10.1371/journal.pone.0124612
Pubmed ID
Authors

George Pentheroudakis, Georgia Raptou, Vassiliki Kotoula, Ralph M. Wirtz, Eleni Vrettou, Vasilios Karavasilis, Georgia Gourgioti, Chryssa Gakou, Konstantinos N. Syrigos, Evangelos Bournakis, Grigorios Rallis, Ioannis Varthalitis, Eleni Galani, Georgios Lazaridis, George Papaxoinis, Dimitrios Pectasides, Gerasimos Aravantinos, Thomas Makatsoris, Konstantine T. Kalogeras, George Fountzilas

Abstract

Although host immune response is an emerging prognostic factor for colorectal cancer, there is no consensus on the optimal methodology, surrogate markers or tissue for study. Tumour blocks were prospectively collected from 344 patients with stage II/III colorectal cancer (CRC) treated with adjuvant chemotherapy. Whole section lymphocytic infiltration was studied along with mRNA expression of CD3Z, CD8, CD4, CXCL9, CXCL13, IGHM, FOXP3, SNAI2 and ESR1 by qRT-qPCR in tissue microarray (TMA) cores from the centre of tumour, invasive margin and adjacent normal mucosa. Lymphocytic infiltration, deficient MMR (10.9%), KRAS (40.7%) and BRAF (4.9%) mutations or single mRNA gene expression were not prognostic. Tumour ESR1 gene expression (Hazard Ratio [HR] for relapse 2.33, 95% CI 1.35-4.02; HR for death 1.74, 95% CI 1.02-2.97) and absence of necrosis (HR for relapse 1.71, 95% CI 1.05-2.71; HR for death 1.98, 95% CI 1.14-3.43) were adverse prognostic features. We used CD3Z and CD8 expression in order to devise the mRNA-based Immune Score (mIS) and proceeded to partitioning analysis in 267 patients, with age, stage, tumour site (Right vs Left CRC), KRAS mutation and tumour mIS as input factors. Only in patients with stage III right-sided colon cancer, a low immune response was associated with inferior disease-free survival (mIS-low, HR for relapse 2.28, 95% CI 1.05-8.02). No prognostic significance was seen for tumour mIS in any other stage or site of CRC, or for a similar mIS score derived from adjacent normal mucosa. Independent adverse prognostic significance was retained in multivariable analysis for absence of necrosis, tumour ESR1 expression in all patients and low tumour mIS in stage III right-sided CRC. In localised CRC, mRNA-based CD3Z/CD8 profiling of tumour immune response may have stage, site and tissue-specific prognostic significance, along with ESR1 expression. ANZCTR.org.au ACTRN12610000509066.

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The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 75 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 1%
Unknown 74 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 15%
Researcher 11 15%
Student > Master 10 13%
Student > Bachelor 6 8%
Other 5 7%
Other 12 16%
Unknown 20 27%
Readers by discipline Count As %
Medicine and Dentistry 21 28%
Biochemistry, Genetics and Molecular Biology 12 16%
Nursing and Health Professions 7 9%
Agricultural and Biological Sciences 5 7%
Immunology and Microbiology 3 4%
Other 3 4%
Unknown 24 32%
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 05 February 2016.
All research outputs
#20,303,950
of 22,842,950 outputs
Outputs from PLOS ONE
#173,980
of 194,886 outputs
Outputs of similar age
#222,141
of 264,472 outputs
Outputs of similar age from PLOS ONE
#5,922
of 6,862 outputs
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