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. 2019 Apr 27;20(9):2082.
doi: 10.3390/ijms20092082.

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

Chiara Zanusso  1 , Eva Dreussi  2 , Roberto Bortolus  3 , Chiara Romualdi  4 , Sara Gagno  5 , Elena De Mattia  6 , Loredana Romanato  7 , Franca Sartor  8 , Luca Quartuccio  9 , Erika Cecchin  10 , Giuseppe Toffoli  11
Affiliations

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

Chiara Zanusso et al. Int J Mol Sci. .

Abstract

Up to 30-50% 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' 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 n = 418; a replication set n = 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 (p-value < 0.05, q-value < 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 PDL1 gene (rs4143815) was the unique potential genetic variant of 10 year BCR (training set: p = 0.003, HR (95% CI) = 0.58 (0.41-0.83); replication set: p = 0.063, HR (95% CI) = 0.52 (0.26-1.04)) that was significantly associated with 5 year BCR (training set: p = 0.009, HR (95% CI) = 0.59 (0.40-0.88); replication set: p = 0.036, HR (95% CI) = 0.39 (0.16-0.94)). No biomarkers of OS were replicated. rs4143815-PDL1 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.

Keywords: biochemical recurrence; biomarker; immunogenetics; prostate cancer; radiotherapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier curves of 10 year BCR according to rs4143815-PDL1 in the training set (A) and in the replication set (B) and Kaplan–Meier curves of 5 year BCR after RT according to rs4143815-PDL1 in the training set (C) and in the replication set (D).
Figure 2
Figure 2
Study design. Firstly, analyses were performed on a discovery set and secondly, in a replication set. At the end of the study, rs4143815-PDL1 arose as a new potential immunogenetic biomarker of 10 year and 5 year BCR in locally advanced prostate cancer. Abbreviations: PCa, prostate cancer; BCR: biochemical recurrence; OS: overall survival; pts: patients.
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References

    1. Xie W., Regan M.M., Buyse M., Halabi S., Kantoff P.W., Sartor O., Soule H., Clarke N.W., Collette L., Dignam J.J., et al. Metastasis-Free Survival Is a Strong Surrogate of Overall Survival in Localized Prostate Cancer. J. Clin. Oncol. 2017;35:3097–3104. doi: 10.1200/JCO.2017.73.9987. - DOI - PMC - PubMed
    1. Williams S. Surrogate endpoints in early prostate cancer research. Transl. Androl. Urol. 2018;7:472–482. doi: 10.21037/tau.2018.05.10. - DOI - PMC - PubMed
    1. De Langhe S., De Ruyck K., Ost P., Fonteyne V., Werbrouck J., De Meerleer G., De Neve W., Thierens H. Acute radiation-induced nocturia in prostate cancer patients is associated with pretreatment symptoms, radical prostatectomy, and genetic markers in the TGFβ1 gene. Int. J. Radiat. Oncol. Biol. Phys. 2013;85:393–399. doi: 10.1016/j.ijrobp.2012.02.061. - DOI - PubMed
    1. Langsenlehner T., Thurner E.M., Renner W., Gerger A., Kapp K.S., Langsenlehner U. Association of genetic variants in VEGF-A with clinical recurrence in prostate cancer patients treated with definitive radiotherapy. Strahlenther. Onkol. 2014;190:364–369. doi: 10.1007/s00066-013-0503-2. - DOI - PubMed
    1. Renner W., Langsenlehner U., Krenn-Pilko S., Eder P., Langsenlehner T. BCL2 genotypes and prostate cancer survival. Strahlenther. Onkol. 2017;193:466–471. doi: 10.1007/s00066-017-1126-9. - DOI - PMC - PubMed