rs4143815-<i>PDL1</i>, a New Potential Immunogenetic Biomarker of Biochemical Recurrence in Locally Advanced Prostate Cancer after Radiotherapy

• Main Authors: Chiara Zanusso, Eva Dreussi, Roberto Bortolus, Chiara Romualdi, Sara Gagno, Elena De Mattia, Loredana Romanato, Franca Sartor, Luca Quartuccio, Erika Cecchin, Giuseppe Toffoli
• Format: Article
• Language: English
• Published: MDPI AG 2019-04-01
• Series: International Journal of Molecular Sciences
• Subjects: prostate cancer; immunogenetics; biomarker; radiotherapy; biochemical recurrence
• Online Access: https://www.mdpi.com/1422-0067/20/9/2082

Up to 30&#8722;50% of patients with locally advanced prostate cancer (PCa) undergoing radiotherapy (RT) experience biochemical recurrence (BCR). The immune system affects the RT response. Immunogenetics could define new biomarkers for personalization of PCa patients&#8217; treatment. The aim of this study is to define the immunogenetic biomarkers of 10 year BCR (primary aim), 10 year overall survival (OS) and 5 year BCR (secondary aims). In this mono-institutional retrospective study, 549 Caucasian patients (a discovery set <i>n</i> = 418; a replication set <i>n</i> = 131) were affected by locally advanced PCa and homogeneously treated with RT. In the training set, associations were made between 447 SNPs in 77 genes of the immune system; and 10 year BCR and 10 year OS were tested through a multivariate Cox proportional hazard model. Significant SNPs (<i>p</i>-value &lt; 0.05, <i>q</i>-value &lt; 0.15) were analyzed in the replication set. Replicated SNPs were tested for 5 year BCR in both sets of patients. A polymorphism in the <i>PDL1</i> gene (rs4143815) was the unique potential genetic variant of 10 year BCR (training set: <i>p</i> = 0.003, HR (95% CI) = 0.58 (0.41&#8722;0.83); replication set: <i>p</i> = 0.063, HR (95% CI) = 0.52 (0.26&#8722;1.04)) that was significantly associated with 5 year BCR (training set: <i>p</i> = 0.009, HR (95% CI) = 0.59 (0.40&#8722;0.88); replication set: <i>p</i> = 0.036, HR (95% CI) = 0.39 (0.16&#8722;0.94)). No biomarkers of OS were replicated. rs4143815-<i>PDL1</i> arose as a new immunogenetic biomarker of BCR in PCa, giving new insights into the RT/immune system interaction, which could be potentially useful in new approaches using anti-PDL1 therapies for PCa.