Deletions on Chromosome Y and Downregulation of the SRY Gene in Tumor Tissue Are Associated with Worse Survival of Glioblastoma Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. IDH1/2 and MGMT Analysis
2.3. Droplet Digital PCR (ddPCR)
2.4. Statistical Analysis
2.5. Gene Set Enrichment Analysis (GSEA)
3. Results
3.1. Copy Number Alterations
3.2. Influence of Gene Dosage Alterations and mRNA Expression on Survival
3.3. SRY Loss
3.4. Gene Set Enrichment Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
GBM | Glioblastoma |
IDH | Isocitrate dehydrogenase |
LOY | Loss of chromosome Y |
TCGA | The Cancer Genome Atlas |
MGMT | O-6-methylguanine-DNA methyltransferase |
SRY | Sex determining region Y gene |
ddPCR | Droplet digital PCR |
OS | Overall survival |
CN | Copy number |
GSEA | Gene Set Enrichment Analysis |
ZFY | Zinc finger protein Y-linked |
AMELY | Amelogenin Y-linked |
ARSEP1 | Arylsulfatase L pseudogene 1 |
USP9Y | Ubiquitin specific peptidase 9 Y-Linked |
UTY | Ubiquitously transcribed tetratricopeptide repeat containing, Y-Linked |
TMSB4Y | Thymosin beta 4 Y-linked |
NLGN4Y | Neuroligin 4 Y-linked |
KDM5D | Lysine demethylase 5D |
EIF1AY | Eukaryotic translation initiation factor 1A Y-linked |
LGG | Lower grade gliomas |
c-Myc | MYC proto-oncogene |
ErbB | Epidermal growth factor receptor family |
EGFR | Epidermal growth factor receptor |
PDGFR | Platelet derived growth factor receptor |
VEGFR1/2 | Vascular endothelial growth factor receptor 1 and 2 |
PI3K | Phosphoinositide 3 kinase |
Akt | Protein kinase B |
IGF1 | Insulin like growth factor 1 |
eIF | Eukaryotic translation initiation factor |
Fas | Fas cell surface death receptor |
Rac1 | Rac family small GTPase 1 |
FOXO | Forkhead box O1 |
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Characteristics | Category | Number of Patients | Percentage |
---|---|---|---|
Age, years | ≤60 | 64 | 61% |
>60 | 41 | 39% | |
Surgery | Biopsy | 15 | 14% |
Partial resection | 24 | 23% | |
Large total resection | 66 | 63% | |
Preoperative performance status WHO | 0–1 | 83 | 79% |
2–3 | 19 | 18% | |
Missing | 3 | 3% | |
RT dose (Gray) | 34 a | 7 | 6.7% |
40–50 b | 8 | 7.6% | |
54–60 | 89 | 84.7% | |
Missing | 1 | 1% | |
MGMT | Methylated | 36 | 65.7% |
Unmethylated | 69 | 34.3% | |
SRY CN | ≤0.6 | 12 | 11.4% |
>0.6 | 92 | 87.6% | |
Missing | 1 | 0.95% |
Variables | Compared Groups | Hazard Ratio (95% Cl) | p-Value |
---|---|---|---|
Age | >60 vs. ≤60 | 1.702 (1.1–2.633) | 0.017 * |
Preoperative performance status (WHO) | 2-3 vs. 0-1 | 0.937 (0.553–1.588) | 0.810 |
Type of surgery | Biopsy/partial vs. large total | 1.131 (0.736–1.740) | 0.574 |
MGMT status | Unmethylated vs. methylated | 2.071 (1.302–3.294) | 0.002 * |
CN of SRY | ≤0.597 vs. >0.597 | 3.352 (1.695–6.629) | 0.001 * |
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Łysiak, M.; Smits, A.; Roodakker, K.R.; Sandberg, E.; Dimberg, A.; Mudaisi, M.; Bratthäll, C.; Strandeus, M.; Milos, P.; Hallbeck, M.; et al. Deletions on Chromosome Y and Downregulation of the SRY Gene in Tumor Tissue Are Associated with Worse Survival of Glioblastoma Patients. Cancers 2021, 13, 1619. https://doi.org/10.3390/cancers13071619
Łysiak M, Smits A, Roodakker KR, Sandberg E, Dimberg A, Mudaisi M, Bratthäll C, Strandeus M, Milos P, Hallbeck M, et al. Deletions on Chromosome Y and Downregulation of the SRY Gene in Tumor Tissue Are Associated with Worse Survival of Glioblastoma Patients. Cancers. 2021; 13(7):1619. https://doi.org/10.3390/cancers13071619
Chicago/Turabian StyleŁysiak, Małgorzata, Anja Smits, Kenney Roy Roodakker, Elisabeth Sandberg, Anna Dimberg, Munila Mudaisi, Charlotte Bratthäll, Michael Strandeus, Peter Milos, Martin Hallbeck, and et al. 2021. "Deletions on Chromosome Y and Downregulation of the SRY Gene in Tumor Tissue Are Associated with Worse Survival of Glioblastoma Patients" Cancers 13, no. 7: 1619. https://doi.org/10.3390/cancers13071619