IFNL4 -ΔG Allele Is Associated with an Interferon Signature in Tumors and Survival of African-American Men with Prostate Cancer

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Wei TangStefan Ambs

Abstract

Purpose: Men of African ancestry experience an excessive prostate cancer mortality that could be related to an aggressive tumor biology. We previously described an immune-inflammation signature in prostate tumors of African-American (AA) patients. Here, we further deconstructed this signature and investigated its relationships with tumor biology, survival, and a common germline variant in the IFNλ4 (IFNL4) gene.Experimental Design: We analyzed gene expression in prostate tissue datasets and performed genotype and survival analyses. We also overexpressed IFNL4 in human prostate cancer cells.Results: We found that a distinct interferon (IFN) signature that is analogous to the previously described "IFN-related DNA damage resistance signature" (IRDS) occurs in prostate tumors. Evaluation of two independent patient cohorts revealed that IRDS is detected about twice as often in prostate tumors of AA than European-American men. Furthermore, analysis in TCGA showed an association of increased IRDS in prostate tumors with decreased disease-free survival. To explain these observations, we assessed whether IRDS is associated with an IFNL4 germline variant (rs368234815-ΔG) that controls production of IFNλ4, a type III IFN, and is most comm...Continue Reading

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Citations

Apr 19, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Thomas R O'BrienLudmila Prokunina-Olsson
May 10, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Ludmila Prokunina-Olsson
Jun 5, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Sreedhar Chinnaswamy, Marek L Kowalski
Jun 5, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Thomas R O'Brien, Sarah S Jackson
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Dec 10, 2020·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Wei TangStefan Ambs
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Jul 18, 2021·Critical Reviews in Oncology/hematology·Julieta Abraham-MirandaKosj Yamoah
Jul 16, 2021·Journal of the National Cancer Institute·Maeve KielyStefan Ambs
Aug 28, 2021·Cancers·Maeve KielyStefan Ambs
Jun 26, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Carla CalaguaDavid J Einstein
Nov 20, 2021·Current Opinion in Urology·Sujit S NairAshutosh K Tewari

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