XKR8 is a promising potential prognostic marker in glioblastoma multiforme patients

Date 23 November 2019
Event ESMO Asia Congress 2019
Session Poster display session
Topics Central Nervous System Malignancies
Personalised/Precision Medicine
Presenter Kristina Havrysh
Citation Annals of Oncology (2019) 30 (suppl_9): ix122-ix130. 10.1093/annonc/mdz431
Authors K.V. Havrysh1, M. Bogdanov2, A.K. Nurgalieva1, R. Kiyamova1
  • 1Biochemistry, Biotechnology And Pharmacology, Institute of Fundamental Medicine and Biology ofKazan Federal University, 420008 - Kazan/RU
  • 2Department Of Biochemistry And Molecular Biology, University of Texas Health Science Center, McGovern Medical School, 77030 - Houston/US

Abstract

Background

The most frequent and aggressive primary brain malignancy in adults is a glioblastoma multiforme (GBM) which is frequently resistant to apoptosis-inducing chemotherapeutic agents. Surface exposure of phosphatidylserine (PS) is a universally recognized apoptotic phenomenon. Although in acute myeloid leukemia and T-cell lymphoma cells Xkr8 mediates PS exposure in response to apoptotic stimuli, the mechanisms underlying the regulation of Xkr8 expression remain unclear. Nevertheless, the loss of Xkr8 in blood cancer cells blocks cell-surface exposure of PS and causes dramatic decreasing of engulfment by phagocytes. Whether Xkr8 is dysregulated in specific cancers and contribute to the survival of patients has not been investigated. This study was aimed to investigate the association of overall survival (OS) and disease-free survival (DFS) with expression and copy number alterations (CNA) of XKR8 gene in GBM patients.

Methods

Data of gene expression, CNA and clinical information from 619 GBM tumors were obtained from TCGA Glioblastoma Multiforme study using the open platform CBioPortal. Among all cases, 572 GBM samples were with CNA (GISTIC 2.0. Values) data and 162 samples were with mRNA expression data (RNA Seq V2 RSEM). Patients were divided into two groups taking into account CNA or expression of mRNA. XKR8 expression was scored as downregulated when mRNA value was lower than the mean expression + standard deviation. XKR8 gene was marked as amplified when CNA value was equal 1 or 2. Kaplan-Meier and log-rank analyses were performed using RStudio.

Results

Survival analysis in GBM patients showed that the OS (p-value=0,015) of the group with downregulated XKR8 mRNA expression (n = 22) was better than of group with normal and upregulated expression (n = 140). Equivalent results have been shown for DFS, where the patients with low XKR8 expression (n = 15) had a weaker risk of disease recurrence (p-value=0,003) than other GBM patients (n = 103). Also, the OS of GBM patients with amplified XKR8 gene (n = 83) was worse (p-value=0,049) than of patients with other CNAs (n = 489).

Conclusions

Thus XKR8 gene can be characterized as prognostic biomarker of survival and disease progression in GBM patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Research Laboratory "Biomarker" IFMB KFU.

Funding

Russian Government Program of Competitive Growth of Kazan Federal University.

Disclosure

All authors have declared no conflicts of interest.