DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Gene Selection
2.2. DNA Methylation Analysis
2.3. Correlation Analysis
2.4. Clinical Data Analysis
2.5. Statistical Analysis
2.6. Ethics Statement
3. Results
3.1. PI3K/AKT Related Genes Are Deregulated in Pancreatic Cancer
3.2. Methylation of PI3K/AKT Related Genes Is Associated with Patients’ Survival
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Pathway | Gene | Pathway Activator (↑) or Repressor (↓) | Probe | Fold-Change | p-Value | Expression Higher |
---|---|---|---|---|---|---|
PI3K/AKT | ITGA4 | ↑ | 205884_at | 2.26 | <0.0001 | Tumour |
205885_s_at | 2.21 | <0.0001 | ||||
SFN | ↑ | 209260_at | 2.64 | 0.000154 | Tumour | |
33322_i_at | 5.65 | <0.0001 | ||||
33323_r_at | 5.47 | <0.0001 | ||||
PPP2R5C | ↓ | 1557718_at | 2.47 | <0.05 | Tumour | |
PIK3CD | ↑ | 203879_at | 2.08 | <0.001 | Tumour | |
ITGA2 | ↑ | 205032_at | 3.07 | <0.0001 | Tumour | |
227314_at | 4.77 | <0.0001 | ||||
PIK3R1 | ↑ | 212239_at | 1.92 | <0.05 | Tumour | |
AKT3 | ↑ | 212609_s_at | 1.9 | <0.0001 | Tumour | |
222880_at | 1.58 | <0.0001 | ||||
EIF4EBP1 | ↑ | 221539_at | −2.46 | <0.0001 | Normal Tissue | |
INPP5D | ↓ | 203332_s_at | 2.11 | <0.001 | Tumour | |
JAK2 | ↓ | 205842_s_at | 2.05 | <0.0001 | Tumour | |
MRAS | ↑ | 225185_at | 1.84 | <0.0001 | Tumour | |
MAP2K2 | ↓ | 213490_s_at | −2.03 | <0.0001 | Normal Tissue | |
MAP3K8 | ↑ | 205027_s_at | 3.48 | <0.0001 | Tumour | |
RAC2 | ↑ | 213603_s_at | 3.51 | <0.0001 | Tumour | |
PTEN | ↓ | 1556006_s_at | 3.88 | <0.05 | Tumour |
Pathway | Gene | Probe | CpG Location | Mean β Normal Tissue | Mean β Tumour Tissue | |Δβ| | AUC | Methylation Higher | p-Value |
---|---|---|---|---|---|---|---|---|---|
PI3K/AKT | ITGA4 | cg25652029 | 5′UTR; 1stExon | 0.05121 | 0.263 | 0.21179 | 0.8628 | Tumour | 0.0004 |
cg06952671 | 5′UTR;1stExon | 0.02106 | 0.2828 | 0.26174 | 0.9434 | <0.0001 | |||
cg21995919 | 5′UTR; 1stExon | 0.04834 | 0.2738 | 0.22546 | 0.8967 | 0.0003 | |||
cg25024074 | 1stExon | 0.07445 | 0.3427 | 0.26825 | 0.9046 | 0.0003 | |||
SFN | cg17330303 | 5′UTR; 1stExon | 0.8891 | 0.6121 | 0.277 | 0.9087 | Normal Tissue | 0.0002 | |
cg13466284 | 5′UTR; 1stExon | 0.7461 | 0.5177 | 0.2284 | 0.9183 | 0.0001 | |||
cg07786675 | 1stExon | 0.8341 | 0.5408 | 0.2933 | 0.9208 | 0.0001 | |||
cg13374701 | 1stExon | 0.9243 | 0.677 | 0.2473 | 0.9197 | 0.0001 | |||
cg12583970 | 1stExon | 0.8847 | 0.6573 | 0.2274 | 0.9396 | <0.0001 | |||
PIK3CD | cg07805542 | Gene body | 0.6719 | 0.3175 | 0.3544 | 0.8754 | Normal Tissue | 0.0005 | |
ITGA2 | cg08446038 | Gene body | 0.547 | 0.2715 | 0.2755 | 0.8298 | Normal Tissue | 0.0023 | |
PIK3R1 | cg15021292 | TSS1500 | 0.7572 | 0.5152 | 0.242 | 0.9063 | Normal Tissue | 0.0002 |
Pathway | Gene Symbol | Probe | Spearman r | p-Value | Correlation |
---|---|---|---|---|---|
PI3K/AKT | ITGA4 | cg25652029 | −0.3868 | <0.0001 | Negative |
cg06952671 | −0.3615 | <0.0001 | Negative | ||
cg21995919 | −0.2992 | <0.0001 | Negative | ||
cg25024074 | −0.3396 | <0.0001 | Negative | ||
SFN | cg17330303 | −0.5648 | <0.0001 | Negative | |
cg13466284 | −0.5833 | <0.0001 | Negative | ||
cg07786675 | −0.5519 | <0.0001 | Negative | ||
cg13374701 | −0.6049 | <0.0001 | Negative | ||
cg12583970 | −0.5921 | <0.0001 | Negative | ||
PIK3CD | cg07805542 | 0.2534 | 0.0011 | Positive | |
ITGA2 | cg08446038 | −0.4785 | <0.0001 | Negative | |
PIK3R1 | cg15021292 | 0.2214 | 0.0045 | Positive |
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Faleiro, I.; Roberto, V.P.; Demirkol Canli, S.; Fraunhoffer, N.A.; Iovanna, J.; Gure, A.O.; Link, W.; Castelo-Branco, P. DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study. Cancers 2021, 13, 6354. https://doi.org/10.3390/cancers13246354
Faleiro I, Roberto VP, Demirkol Canli S, Fraunhoffer NA, Iovanna J, Gure AO, Link W, Castelo-Branco P. DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study. Cancers. 2021; 13(24):6354. https://doi.org/10.3390/cancers13246354
Chicago/Turabian StyleFaleiro, Inês, Vânia Palma Roberto, Secil Demirkol Canli, Nicolas A. Fraunhoffer, Juan Iovanna, Ali Osmay Gure, Wolfgang Link, and Pedro Castelo-Branco. 2021. "DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study" Cancers 13, no. 24: 6354. https://doi.org/10.3390/cancers13246354