Characterization and evaluation of gene fusions as a measure of genetic instability and disease prognosis in prostate cancer

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Carolin Schimmelpfennig - , Fraunhofer-Institut für Zelltherapie und Immunologie (Autor:in)
  • Michael Rade - , Fraunhofer-Institut für Zelltherapie und Immunologie (Autor:in)
  • Susanne Füssel - , Klinik und Poliklinik für Urologie (Autor:in)
  • Dennis Löffler - , Fraunhofer-Institut für Zelltherapie und Immunologie (Autor:in)
  • Conny Blumert - , Fraunhofer-Institut für Zelltherapie und Immunologie (Autor:in)
  • Catharina Bertram - , Fraunhofer-Institut für Zelltherapie und Immunologie (Autor:in)
  • Angelika Borkowetz - , Klinik und Poliklinik für Urologie (Autor:in)
  • Dominik J. Otto - , Fraunhofer-Institut für Zelltherapie und Immunologie (Autor:in)
  • Sven Holger Puppel - , Fraunhofer-Institut für Zelltherapie und Immunologie (Autor:in)
  • Pia Hönscheid - , Institut für Pathologie (Autor:in)
  • Ulrich Sommer - , Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Gustavo B. Baretton - , Institut für Pathologie (Autor:in)
  • Ulrike Köhl - , Fraunhofer-Institut für Zelltherapie und Immunologie, Universität Leipzig (Autor:in)
  • Manfred Wirth - , Klinik und Poliklinik für Urologie (Autor:in)
  • Christian Thomas - , Klinik und Poliklinik für Urologie (Autor:in)
  • Friedemann Horn - , Fraunhofer-Institut für Zelltherapie und Immunologie (Autor:in)
  • Markus Kreuz - , Fraunhofer-Institut für Zelltherapie und Immunologie (Autor:in)
  • Kristin Reiche - , Fraunhofer-Institut für Zelltherapie und Immunologie, Universität Leipzig (Autor:in)

Abstract

Background: Prostate cancer (PCa) is one of the most prevalent cancers worldwide. The clinical manifestations and molecular characteristics of PCa are highly variable. Aggressive types require radical treatment, whereas indolent ones may be suitable for active surveillance or organ-preserving focal therapies. Patient stratification by clinical or pathological risk categories still lacks sufficient precision. Incorporating molecular biomarkers, such as transcriptome-wide expression signatures, improves patient stratification but so far excludes chromosomal rearrangements. In this study, we investigated gene fusions in PCa, characterized potential novel candidates, and explored their role as prognostic markers for PCa progression. Methods: We analyzed 630 patients in four cohorts with varying traits regarding sequencing protocols, sample conservation, and PCa risk group. The datasets included transcriptome-wide expression and matched clinical follow-up data to detect and characterize gene fusions in PCa. With the fusion calling software Arriba, we computationally predicted gene fusions. Following detection, we annotated the gene fusions using published databases for gene fusions in cancer. To relate the occurrence of gene fusions to Gleason Grading Groups and disease prognosis, we performed survival analyses using the Kaplan–Meier estimator, log-rank test, and Cox regression. Results: Our analyses identified two potential novel gene fusions, MBTTPS2,L0XNC01::SMS and AMACR::AMACR. These fusions were detected in all four studied cohorts, providing compelling evidence for the validity of these fusions and their relevance in PCa. We also found that the number of gene fusions detected in a patient sample was significantly associated with the time to biochemical recurrence in two of the four cohorts (log-rank test, p-value < 0.05 for both cohorts). This was also confirmed after adjusting the prognostic model for Gleason Grading Groups (Cox regression, p-values < 0.05). Conclusions: Our gene fusion characterization workflow revealed two potential novel fusions specific for PCa. We found evidence that the number of gene fusions was associated with the prognosis of PCa. However, as the quantitative correlations were only moderately strong, further validation and assessment of clinical value is required before potential application.

Details

OriginalspracheEnglisch
Aufsatznummer575
Seitenumfang20
FachzeitschriftBMC cancer
Jahrgang23
Ausgabenummer1
PublikationsstatusVeröffentlicht - Dez. 2023
Peer-Review-StatusJa

Externe IDs

PubMed 37349736

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete

Schlagwörter

  • Biomarker, Gene fusion, Genomic instability, Molecular diagnostic testing, Molecular pathology, Next-generation sequencing, Prognosis, Prostate cancer, Transcriptome, Humans, Male, Gene Fusion, Biomarkers, Tumor/genetics, Neoplasm Grading, Prostatic Neoplasms/pathology

Bibliotheksschlagworte