In silico and Ex vivo approaches identify a role for toll-like receptor 4 in colorectal cancer

Daniel A Sussman, Rebeca Santaolalla, Pablo A. Bejarano, Monica Garcia-Buitrago, Maria T. Perez, Maria T Abreu, Jennifer Clarke

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Inflammation increases the risk of colorectal cancer (CRC). We and others have described a role for TLR4, the receptor for LPS, in colon cancer. To explore the relationships between TLR4 expression and CRC, we combined the strength of transcriptome array data and immunohistochemical (IHC) staining. Methods. TLR4 signal intensity was scored in the stromal and epithelial compartments. Detection of differential expression between conditions of interest was performed using linear models, Cox proportional hazards models, and empirical Bayes methods. Results: A strong association between TLR4 expression and survival was noted, though a dichotomous relationship between survival and specific TLR4 transcripts was observed. Increasing TLR4 expression was seen with advancing tumor stage and was also over-expressed in some adenomas. IHC staining confirmed the positive relationship between TLR4 staining score in the CRC tumor stroma and epithelium with tumor stage, with up to 47% of colon cancer stroma positive for TLR4 staining. Increased TLR4 expression by IHC was also marginally associated with decreased survival. We now also describe that pericryptal myofibroblasts are responsible for a portion of the TLR4 stromal staining. Conclusions: Increased TLR4 expression occurs early in colonic neoplasia. TLR4 is associated with the important cancer-related outcomes of survival and stage.

Original languageEnglish
Article number45
JournalJournal of Experimental and Clinical Cancer Research
Volume33
Issue number1
DOIs
StatePublished - May 22 2014

Fingerprint

Toll-Like Receptor 4
Computer Simulation
Colorectal Neoplasms
Staining and Labeling
Colonic Neoplasms
Neoplasms
Myofibroblasts
Transcriptome
Proportional Hazards Models
Adenoma
Linear Models
Epithelium
Inflammation

Keywords

  • Bioinformatics
  • Colon cancer
  • Colorectal cancer
  • Immunohistochemistry
  • TLR4
  • Transcriptome

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

In silico and Ex vivo approaches identify a role for toll-like receptor 4 in colorectal cancer. / Sussman, Daniel A; Santaolalla, Rebeca; Bejarano, Pablo A.; Garcia-Buitrago, Monica; Perez, Maria T.; Abreu, Maria T; Clarke, Jennifer.

In: Journal of Experimental and Clinical Cancer Research, Vol. 33, No. 1, 45, 22.05.2014.

Research output: Contribution to journalArticle

@article{d22b37a51a6e4a319edf7eb9c4153c59,
title = "In silico and Ex vivo approaches identify a role for toll-like receptor 4 in colorectal cancer",
abstract = "Background: Inflammation increases the risk of colorectal cancer (CRC). We and others have described a role for TLR4, the receptor for LPS, in colon cancer. To explore the relationships between TLR4 expression and CRC, we combined the strength of transcriptome array data and immunohistochemical (IHC) staining. Methods. TLR4 signal intensity was scored in the stromal and epithelial compartments. Detection of differential expression between conditions of interest was performed using linear models, Cox proportional hazards models, and empirical Bayes methods. Results: A strong association between TLR4 expression and survival was noted, though a dichotomous relationship between survival and specific TLR4 transcripts was observed. Increasing TLR4 expression was seen with advancing tumor stage and was also over-expressed in some adenomas. IHC staining confirmed the positive relationship between TLR4 staining score in the CRC tumor stroma and epithelium with tumor stage, with up to 47{\%} of colon cancer stroma positive for TLR4 staining. Increased TLR4 expression by IHC was also marginally associated with decreased survival. We now also describe that pericryptal myofibroblasts are responsible for a portion of the TLR4 stromal staining. Conclusions: Increased TLR4 expression occurs early in colonic neoplasia. TLR4 is associated with the important cancer-related outcomes of survival and stage.",
keywords = "Bioinformatics, Colon cancer, Colorectal cancer, Immunohistochemistry, TLR4, Transcriptome",
author = "Sussman, {Daniel A} and Rebeca Santaolalla and Bejarano, {Pablo A.} and Monica Garcia-Buitrago and Perez, {Maria T.} and Abreu, {Maria T} and Jennifer Clarke",
year = "2014",
month = "5",
day = "22",
doi = "10.1186/1756-9966-33-45",
language = "English",
volume = "33",
journal = "Journal of Experimental and Clinical Cancer Research",
issn = "0392-9078",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - In silico and Ex vivo approaches identify a role for toll-like receptor 4 in colorectal cancer

AU - Sussman, Daniel A

AU - Santaolalla, Rebeca

AU - Bejarano, Pablo A.

AU - Garcia-Buitrago, Monica

AU - Perez, Maria T.

AU - Abreu, Maria T

AU - Clarke, Jennifer

PY - 2014/5/22

Y1 - 2014/5/22

N2 - Background: Inflammation increases the risk of colorectal cancer (CRC). We and others have described a role for TLR4, the receptor for LPS, in colon cancer. To explore the relationships between TLR4 expression and CRC, we combined the strength of transcriptome array data and immunohistochemical (IHC) staining. Methods. TLR4 signal intensity was scored in the stromal and epithelial compartments. Detection of differential expression between conditions of interest was performed using linear models, Cox proportional hazards models, and empirical Bayes methods. Results: A strong association between TLR4 expression and survival was noted, though a dichotomous relationship between survival and specific TLR4 transcripts was observed. Increasing TLR4 expression was seen with advancing tumor stage and was also over-expressed in some adenomas. IHC staining confirmed the positive relationship between TLR4 staining score in the CRC tumor stroma and epithelium with tumor stage, with up to 47% of colon cancer stroma positive for TLR4 staining. Increased TLR4 expression by IHC was also marginally associated with decreased survival. We now also describe that pericryptal myofibroblasts are responsible for a portion of the TLR4 stromal staining. Conclusions: Increased TLR4 expression occurs early in colonic neoplasia. TLR4 is associated with the important cancer-related outcomes of survival and stage.

AB - Background: Inflammation increases the risk of colorectal cancer (CRC). We and others have described a role for TLR4, the receptor for LPS, in colon cancer. To explore the relationships between TLR4 expression and CRC, we combined the strength of transcriptome array data and immunohistochemical (IHC) staining. Methods. TLR4 signal intensity was scored in the stromal and epithelial compartments. Detection of differential expression between conditions of interest was performed using linear models, Cox proportional hazards models, and empirical Bayes methods. Results: A strong association between TLR4 expression and survival was noted, though a dichotomous relationship between survival and specific TLR4 transcripts was observed. Increasing TLR4 expression was seen with advancing tumor stage and was also over-expressed in some adenomas. IHC staining confirmed the positive relationship between TLR4 staining score in the CRC tumor stroma and epithelium with tumor stage, with up to 47% of colon cancer stroma positive for TLR4 staining. Increased TLR4 expression by IHC was also marginally associated with decreased survival. We now also describe that pericryptal myofibroblasts are responsible for a portion of the TLR4 stromal staining. Conclusions: Increased TLR4 expression occurs early in colonic neoplasia. TLR4 is associated with the important cancer-related outcomes of survival and stage.

KW - Bioinformatics

KW - Colon cancer

KW - Colorectal cancer

KW - Immunohistochemistry

KW - TLR4

KW - Transcriptome

UR - http://www.scopus.com/inward/record.url?scp=84902319520&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902319520&partnerID=8YFLogxK

U2 - 10.1186/1756-9966-33-45

DO - 10.1186/1756-9966-33-45

M3 - Article

C2 - 24887394

AN - SCOPUS:84902319520

VL - 33

JO - Journal of Experimental and Clinical Cancer Research

JF - Journal of Experimental and Clinical Cancer Research

SN - 0392-9078

IS - 1

M1 - 45

ER -