Cell-Free DNA Sequencing Reveals Gene Variants in DNA Damage Repair Genes Associated with Prognosis of Prostate Cancer Patients

Lieb V, Abdulrahman A, Weigelt K, Hauch S, Gombert M, Guzman J, Bellut L, Goebell P, Stöhr R, Hartmann A, Wullich B, Taubert H, Wach S (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Cells MDPI

Book Volume: 11

Article Number: 3618

Journal Issue: 22

DOI: 10.3390/cells11223618

Abstract

In the present study, we further analyzed the data obtained in our previous study, where we investigated the cell-free DNA (cfDNA) of 34 progressive prostate cancer patients via targeted sequencing. Here, we studied the occurrence and prognostic impact of sequence variants according to their clinical pathological significance (CPS) or their functional impact (FI) in 23 DNA damage repair (DDR) genes with a focus on the ATM serine/threonine kinase gene (ATM). All patients had at least one DDR gene with a CPS or FI variant. Kaplan-Meier analysis indicated that the group with a higher number of CPS variants in DDR genes had a shorter time to treatment change (TTC) compared to the group with a lower number of CPS variants (p = 0.038). Analysis of each DDR gene revealed that CPS variants in the ATM gene and FI variants in the nibrin (NBN) gene showed a shorter TTC (p = 0.034 and p = 0.042). In addition, patients with CPS variants in the ATM gene had shorter overall survival (OS; p = 0.022) and disease-specific survival (DSS; p = 0.010) than patients without these variants. Interestingly, patients with CPS variants in seven DDR genes possessed a better OS (p = 0.008) and DSS (p = 0.009), and patients with FI variants in four DDR genes showed a better OS (p = 0.007) and DSS (p = 0.008). Together, these findings demonstrated that the analysis of cfDNA for gene variants in DDR genes provides prognostic information that may be helpful for future temporal and targeted treatment decisions for advanced PCa patients.

Authors with CRIS profile

Verena Lieb Urologische Klinik Amer Abdulrahman Urologische Klinik Juan Guzman Urologische Klinik Laura Bellut Urologische Klinik Peter Goebell Urologische Klinik Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Bernd Wullich Lehrstuhl für Urologie Helge Taubert Professur für Molekulare Urologie

Involved external institutions

QIAGEN GmbH DE Germany (DE)

How to cite

APA:

Lieb, V., Abdulrahman, A., Weigelt, K., Hauch, S., Gombert, M., Guzman, J.,... Wach, S. (2022). Cell-Free DNA Sequencing Reveals Gene Variants in DNA Damage Repair Genes Associated with Prognosis of Prostate Cancer Patients. Cells, 11(22). https://doi.org/10.3390/cells11223618

MLA:

Lieb, Verena, et al. "Cell-Free DNA Sequencing Reveals Gene Variants in DNA Damage Repair Genes Associated with Prognosis of Prostate Cancer Patients." Cells 11.22 (2022).

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