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High toll-like receptor (TLR) 9 expression is associated with better prognosis in surgically treated pancreatic cancer patients

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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.

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Acknowledgements

We thank Erja Tomperi and Riitta Vuento for expertise in preparation of the immunohistochemical stainings.

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Authors and Affiliations

  1. Department of Pathology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland

    Joni Leppänen, Olli Helminen, Heikki Huhta, Joonas H. Kauppila, Joel Isohookana, Kirsi-Maria Haapasaari & Tuomo J. Karttunen

  2. Department of Surgery, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland

    Joni Leppänen, Olli Helminen, Heikki Huhta, Joonas H. Kauppila, Petri Lehenkari & Juha Saarnio

  3. Medical Research Center Oulu, P.O. Box 5000, 90014, Oulu, Finland

    Joni Leppänen, Olli Helminen, Heikki Huhta, Joonas H. Kauppila, Joel Isohookana, Kirsi-Maria Haapasaari, Petri Lehenkari, Juha Saarnio & Tuomo J. Karttunen

  4. Oulu University Hospital, P.O. Box 21, 90029, Oulu, Finland

    Joni Leppänen, Olli Helminen, Heikki Huhta, Joonas H. Kauppila, Joel Isohookana, Kirsi-Maria Haapasaari, Petri Lehenkari, Juha Saarnio & Tuomo J. Karttunen

  5. Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, 17176, Stockholm, Sweden

    Joonas H. Kauppila

  6. Department of Anatomy and Cell Biology, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland

    Petri Lehenkari

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  1. Joni Leppänen
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Correspondence to Joni Leppänen.

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Funding

This work was supported by grants from the Finnish Cultural Foundation (J. L), Finnish Medical Foundation (J. L), Sigrid Jusélius Foundation (J.H.K.), Mary and Georg C. Ehrnroot Foundation (J.H.K.), Thelma Mäkikyrö Foundation (J.H.K.), Orion Research Foundation (J.H.K.), and Medical Research Center Oulu Focus Group Funding (T.J.K.).

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Leppänen, J., Helminen, O., Huhta, H. et al. High toll-like receptor (TLR) 9 expression is associated with better prognosis in surgically treated pancreatic cancer patients. Virchows Arch 470, 401–410 (2017). https://doi.org/10.1007/s00428-017-2087-1

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