title: High toll-like receptor (TLR) 9 expression is associated with better prognosis in surgically treated pancreatic cancer patients.
abstract: Pancreatic cancer remains one of the deadliest malignancies in the world. Inflammatory response and tumor environment are thought to play a major role in its pathogenesis. Knowledge on TLR expression and impact on patient survival in pancreatic cancer is limited. The study's aim was to clarify the role of different TLRs in pancreatic cancer. TLR2, TLR4, and TLR9 expression was investigated in 65 surgically resected pancreatic ductal adenocarcinoma specimens by immunohistochemistry. The association between TLR expression, clinical parameters, and local inflammatory response to the tumor was assessed using chi-square test. Relation between patient survival and TLR expression was calculated with multivariable Cox regression, adjusted for age, sex, and tumor stage. We found TLR2, TLR4, and TLR9 to be expressed in pancreatic cancer. There was no association between TLR expression and tumor stage, tumor size, lymph node metastasis, or tumor necrosis. Contrary to our initial hypothesis, high cytoplasmic TLR9 expression was associated with longer patient survival, and multivariate analysis identified low TLR9 expression as an independent risk factor for cancer-specific death (HR 3.090, 95% CI 1.673-5.706). The results suggest that high TLR9 expression in pancreatic ductal adenocarcinoma indicates improved prognosis. The prognostic effect of TLR9 might be associated with bacterial exposure, but this needs further evidence.
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland. joni.leppanen@oulu.fi.|Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland. joni.leppanen@oulu.fi.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland. joni.leppanen@oulu.fi.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland. joni.leppanen@oulu.fi.
authors.forename: Joni
authors.identifier: http://orcid.org/0000-0002-6360-021X
authors.initials: J
authors.lastname: Leppänen
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Helminen
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Huhta
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.|Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, 17176, Stockholm, Sweden.
authors.forename: Joonas H
authors.initials: JH
authors.lastname: Kauppila
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Joel
authors.initials: J
authors.lastname: Isohookana
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Kirsi-Maria
authors.initials: KM
authors.lastname: Haapasaari
authors.affiliation: Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.|Department of Anatomy and Cell Biology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Lehenkari
authors.affiliation: Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Saarnio
authors.affiliation: Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland.
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Karttunen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D016016:Proportional Hazards Models; D051217:Toll-Like Receptor 9 / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9
keywords: Inflammatory response; Innate immunity; Pancreatic cancer; Prognosis; Toll-like receptor