Genetic associations of T cell cancer immune response with tumor aggressiveness in localized prostate cancer patients and disease reclassification in an active surveillance cohort

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Determining prostate cancer (PCa) aggressiveness and reclassification are critical events during the treatment of localized disease and for patients undergoing active surveillance (AS). Since T cells play major roles in cancer surveillance and elimination, we aimed to identify genetic biomarkers related to T cell cancer immune response which are predictive of aggressiveness and reclassification risks in localized PCa. The genotypes of 3,586 single nucleotide polymorphisms (SNPs) from T cell cancer immune response pathways were analyzed in 1762 patients with localized disease and 393 who elected AS. The aggressiveness of PCa was defined according to pathological Gleason score (GS) and D’Amico criteria. PCa reclassification was defined according to changes in GS or tumor characteristics during subsequent surveillance biopsies. Functional characterization and analysis of immune phenotypes were also performed. In the localized PCa cohort, seven SNPs were significantly associated with the risk of aggressive disease. In the AS cohort, another eight SNPs were identified as predictors for aggressiveness and reclassification. Rs1687016 of PSMB8 was the most significant predictor of reclassification. Cumulative analysis showed that a genetic score based on the identified SNPs could significantly predict risk of D’Amico high risk disease (P-trend = 2.4E-09), GS4 + 3 disease (P-trend = 1.3E-04), biochemical recurrence (P-trend = 0.01) and reclassification (P-trend = 0.01). In addition, the rs34309 variant was associated with functional somatic mutations in the PI3K/PTEN/AKT/MTOR pathway and tumor lymphocyte infiltration. Our study provides plausible evidence that genetic variations in T cell cancer immune response can influence risks of aggressiveness and reclassification in localized PCa, which may lead to additional biological insight into these outcomes. Abbreviations: PCa, prostate cancer; AS, active surveillance; GS, Gleason score; PSA, prostate specific antigen; TCGA, The Cancer Genome Atlas; SNP, single nucleotide polymorphisms; UFG, unfavorable genotype.

Original languageEnglish (US)
Article numbere1483303
JournalOncoImmunology
Volume8
Issue number1
DOIs
StatePublished - Jan 2 2019

Keywords

  • Aggressiveness
  • PI3K signaling pathway
  • T cell cancer immune response
  • active surveillance
  • biochemical recurrence
  • prostate cancer
  • single nucleotide polymorphisms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

MD Anderson CCSG core facilities

  • Clinical Trials Office

Fingerprint

Dive into the research topics of 'Genetic associations of T cell cancer immune response with tumor aggressiveness in localized prostate cancer patients and disease reclassification in an active surveillance cohort'. Together they form a unique fingerprint.

Cite this