TY - JOUR
T1 - Expression of pattern recognition receptor genes and mortality in patients with colorectal adenocarcinoma
AU - Royse, Kathryn E.
AU - Chen, Liang
AU - Berger, David H.
AU - Ittmann, Michael M.
AU - El-Serag, Hashem B.
AU - Balentine, Courtney J.
AU - Graham, David Y.
AU - Richardson, Peter A.
AU - Rumbaut, Rolando E.
AU - Shen, Xiaoyun
AU - White, Donna L.
AU - Jiao, Li
N1 - Funding Information:
This research was supported in part by the Dan L. Duncan Scholar Award, Gillson Longenbaugh Foundation and Golfers Against Cancer organization (To L. Jiao); Texas Medical Center Digestive Disease Center (P30 DK56338); Houston Veterans Affairs Health Services Research Center of Innovations (CIN13-413), and the Dan L. Duncan Cancer Center Pathology and Histology Core at Baylor College of Medicine (NCI P30-CA125123). We would like to thank Dr. Susan Hilsenbeck at the Lester and Sue Smith Breast Center Baylor College of Medicine, Houston, TX, USA, for her time and review of the methodology and statistical analysis section. We thank Mrs. Sonora Hudson for her edits. The views expressed in this article are those of the authors and do not necessarily represent the views of the funders and the Department of Veterans Affairs.
Publisher Copyright:
© 2017, E-Century Publishing Corporation. All rights reserved.
PY - 2017
Y1 - 2017
N2 - Toll-like receptors (TLRs) and the receptor for advanced glycation end products (AGER) are pattern recognition receptors that regulate intestinal inflammatory homeostasis. However, their relevance in colorectal cancer (CRC) prognosis is unclear. We investigated expression of TLRs, AGER, and interacting proteins in association with CRC mortality in a retrospective cohort study of 65 males diagnosed with primary resectable CRC between 2002 and 2009. Multiplex quantitative nuclease protection assay was used to quantify the expression of 19 genes in archived tissues of tumor and paired adjacent normal mucosa. We evaluated the association between log2 (tumor/ normal) expression ratios for single and combined genes and all-cause mortality using multivariable Cox regression analysis. The false discovery rate adjusted q-value less than 0.10 indicated statistical significance for single gene. Five-year survival time was calculated from diagnosis of CRC to death, lost to follow-up, or December 31, 2014. Compared to paired normal mucosa, expression levels of AGER, IL1A, MYD88, and TLR5 were lower (q = 0.0002); while CXCL8 and S100P were higher (q = 0.0002) in tumor epithelia. Higher tumor expression of IL1A (HRadj =0.68, 95% CI: 0.49-0.94), IL6 (HRadj = 0.70, 95% CI: 0.52-0.94), MyD88 (HRadj = 0.53, 95% CI: 0.30-0.93), and TLR5 (HRadj = 0.71, 95% CI: 0.52-0.98) was associated with higher mortality risk. There was a synergistic effect on lower five-year survival in lower co-expressers of IL-6 and MyD88 (P < 0.0001). Our findings suggest that a TLRs/ MyD88-mediated inflammatory response may play a role in CRC prognosis. The role of pattern recognition receptormediated immunity in CRC mortality warrants further research.
AB - Toll-like receptors (TLRs) and the receptor for advanced glycation end products (AGER) are pattern recognition receptors that regulate intestinal inflammatory homeostasis. However, their relevance in colorectal cancer (CRC) prognosis is unclear. We investigated expression of TLRs, AGER, and interacting proteins in association with CRC mortality in a retrospective cohort study of 65 males diagnosed with primary resectable CRC between 2002 and 2009. Multiplex quantitative nuclease protection assay was used to quantify the expression of 19 genes in archived tissues of tumor and paired adjacent normal mucosa. We evaluated the association between log2 (tumor/ normal) expression ratios for single and combined genes and all-cause mortality using multivariable Cox regression analysis. The false discovery rate adjusted q-value less than 0.10 indicated statistical significance for single gene. Five-year survival time was calculated from diagnosis of CRC to death, lost to follow-up, or December 31, 2014. Compared to paired normal mucosa, expression levels of AGER, IL1A, MYD88, and TLR5 were lower (q = 0.0002); while CXCL8 and S100P were higher (q = 0.0002) in tumor epithelia. Higher tumor expression of IL1A (HRadj =0.68, 95% CI: 0.49-0.94), IL6 (HRadj = 0.70, 95% CI: 0.52-0.94), MyD88 (HRadj = 0.53, 95% CI: 0.30-0.93), and TLR5 (HRadj = 0.71, 95% CI: 0.52-0.98) was associated with higher mortality risk. There was a synergistic effect on lower five-year survival in lower co-expressers of IL-6 and MyD88 (P < 0.0001). Our findings suggest that a TLRs/ MyD88-mediated inflammatory response may play a role in CRC prognosis. The role of pattern recognition receptormediated immunity in CRC mortality warrants further research.
KW - Colorectal neoplasms
KW - Gene expression
KW - Immune
KW - Inflammation
KW - Pattern recognition
KW - Receptor for advanced glycation end-products
KW - Receptors
KW - Survival
KW - Toll-like receptors
KW - Tumor microenvironment
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M3 - Article
AN - SCOPUS:85019598735
SN - 1948-1756
VL - 8
SP - 8
EP - 18
JO - International Journal of Molecular Epidemiology and Genetics
JF - International Journal of Molecular Epidemiology and Genetics
IS - 2
M1 - IJMEG0050564
ER -