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

Autor: Erika Cecchin, Elena De Mattia, Loredana Romanato, Franca Sartor, Chiara Zanusso, Chiara Romualdi, Sara Gagno, Eva Dreussi, Giuseppe Toffoli, Luca Quartuccio, Roberto Bortolus
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Oncology
Kaplan-Meier Estimate
Immunogenetics
B7-H1 Antigen
lcsh:Chemistry
Prostate cancer
0302 clinical medicine
Recurrence
biochemical recurrence
lcsh:QH301-705.5
Spectroscopy
Tumor
breakpoint cluster region
Single Nucleotide
General Medicine
Middle Aged
Prognosis
prostate cancer
Combined Modality Therapy
Computer Science Applications
030220 oncology & carcinogenesis
biomarker
Biomarker (medicine)
Biochemical recurrence
Biomarker
Radiotherapy
Aged
Genotype
Humans
Neoplasm Grading
Neoplasm Staging
Polymorphism
Single Nucleotide
Proportional Hazards Models
Prostatic Neoplasms
Biomarkers
Tumor
medicine.medical_specialty
Single-nucleotide polymorphism
Catalysis
Inorganic Chemistry
03 medical and health sciences
Internal medicine
medicine
Polymorphism
Physical and Theoretical Chemistry
Molecular Biology
radiotherapy
business.industry
Proportional hazards model
Organic Chemistry
Retrospective cohort study
medicine.disease
immunogenetics
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
business
Biomarkers
Zdroj: International Journal of Molecular Sciences
Volume 20
Issue 9
International Journal of Molecular Sciences, Vol 20, Iss 9, p 2082 (2019)
ISSN: 1422-0067
DOI: 10.3390/ijms20092082
Popis: Up to 30&ndash
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&rsquo
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&ndash
0.83)
replication set: p = 0.063, HR (95% CI) = 0.52 (0.26&ndash
1.04)) that was significantly associated with 5 year BCR (training set: p = 0.009, HR (95% CI) = 0.59 (0.40&ndash
0.88)
replication set: p = 0.036, HR (95% CI) = 0.39 (0.16&ndash
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.
Databáze: OpenAIRE
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