title: IFNAR1 is a predictor for overall survival in colorectal cancer and its mRNA expression correlated with IRF7 but not TLR9.
abstract: Toll-like receptor (TLR) 9 plays a role in intestinal inflammation that, in turn, is related to the tumorigenesis of colorectal cancer. Nuclear factor κB (NFκB), and interferon regulatory factor (IRF) 5 and IRF7 can be activated by TLR9 and induce the production of proinflammatory cytokines and type I interferon, respectively. This study investigated the mRNA expressions of TLR9 and its downstream signaling molecules in both the tumor and the normal tissues of colorectal cancer. Eighty-four subjects with colorectal cancer were consecutively recruited at a community-based hospital, and the mRNA expression of TLR9, NFκB, IRF5, IRF7, interleukin 6 (IL6), and interferon α/β/ω receptor 1 (IFNAR1) in the tumor and normal tissue were determined by real-time reverse transcription polymerase chain reaction using TaqMan FAM-labeled MGB probes (Life Technologies, Carlsbad, CA). The tumor had higher percentages of detection of TLR9, IFNAR1, and IL6 mRNA expressions than normal tissue. The absence of detectable TLR9 mRNA expression was associated with an absence of significance in the correlation between IL6 and NFκB or IRF5, but not that between IRF7 and IFNAR1 in both the tumor and the normal tissues. An absence of detectable IFNAR1 mRNA expression in the tumor (hazard ratio: 3.77; 95% confidence interval: 1.22-11.60) and advanced stage (stages III and IV, 7.86; 1.76-35.40) were significant predictors for overall survival. IFNAR1 is a predictor for overall survival and mRNA expression is correlated to IRF7, but not TLR9 in colorectal cancer. The results cast doubt on the usefulness of TLR9 agonist in treating colorectal cancer.
authors.affiliation: From the Department of Pathology (L-CC, T-YH, H-PC, J-RC, C-CH); Division of Colon and Rectal Surgery (C-WF, W-KT); and Department of Internal Medicine (C-CH), Chang Gung Memorial Hospital, Keelung, and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Liang-Che
authors.initials: LC
authors.lastname: Chang
authors.forename: Chung-Wei
authors.initials: CW
authors.lastname: Fan
authors.forename: Wen-Ko
authors.initials: WK
authors.lastname: Tseng
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Chein
authors.forename: Tsan-Yu
authors.initials: TY
authors.lastname: Hsieh
authors.forename: Jim-Ray
authors.initials: JR
authors.lastname: Chen
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Hwang
authors.forename: Chung-Ching
authors.initials: CC
authors.lastname: Hua
mesh_terms: D000367:Age Factors; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000235:genetics; D050835:Interferon Regulatory Factors / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D052002:NF-kappa B p50 Subunit / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D053633:Receptor, Interferon alpha-beta / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051217:Toll-Like Receptor 9 / Q000235:genetics
chemical_list: C507964:IFNAR1 protein, human; C431713:IRF5 protein, human; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D050835:Interferon Regulatory Factors; D015850:Interleukin-6; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D053633:Receptor, Interferon alpha-beta