PODNL1 Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma
Abstract
:1. Introduction
2. Results
2.1. PODNL1 Expression and Methylation in LGG
2.2. Association between PODNL1 Aberrations and Tumor Aggressiveness in LGG
2.3. A Subset of LGGs with Low PODNL1 Methylation Is Associated with Increased Immune Cell Infiltration in the Tumor Microenvironment
2.4. PODNL1 Methylation May Affect Immune Checkpoint Blockade Response in LGG
3. Discussion
4. Materials and Methods
4.1. Tumor Cohort
4.2. PODNL1 Expression and Methylation Analysis
4.3. Survival Analysis
4.4. Differential Gene and Protein Expression Analysis
4.5. Immune Cell Infiltration Analysis
4.6. Immune Checkpoint Blockade (ICB) Therapy Response Prediction
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Univariate Analysis | Multivariate Analysis | ||||||||
---|---|---|---|---|---|---|---|---|---|
Overall Survival | Disease-Free Survival | Overall Survival | Disease-Free Survival | ||||||
CpG loci | Position | HR [95% CI] | p-Value | HR [95% CI] | p-Value | HR [95% CI] | p-Value | HR [95% CI] | p-Value |
cg26498537 | 13929563 | 0.68 [0.48–0.97] | 3.40 × 10−2 | 0.75 [0.56–1.00] | 5.26 × 10−2 | 1.01 [0.69–1.47] | 9.60 ×10−1 | 0.95 [0.70–1.28] | 7.68 × 10−1 |
cg21993464 | 13930493 | 0.60 [0.42–0.87] | 6.56 × 10−3 | 0.82 [0.62–1.09] | 1.89 × 10−1 | 0.91 [0.63–1.33] | 6.57 × 10−1 | 0.99 [0.74–1.33] | 9.82 × 10−1 |
cg14697425 | 13932027 | 1.02 [0.72–1.46] | 8.81 × 10−1 | 1.05 [0.79–1.39] | 7.23 × 10−1 | 1.20 [0.83–1.73] | 3.12 × 10−1 | 1.19 [0.89–1.60] | 2.25 × 10−1 |
cg03417156 | 13932833 | 0.66 [0.46–0.94] | 2.34 × 10−2 | 0.78 [0.58–1.04] | 9.42 × 10−2 | 1.09 [0.73–1.62] | 6.50 × 10−1 | 1.07 [0.79–1.45] | 6.47 × 10−1 |
cg03690334 | 13933004 | 0.57 [0.40–0.82] | 2.43 × 10−3 | 0.72 [0.54–0.96] | 2.62 × 10−2 | 0.72 [0.49–1.04] | 8.64 × 10−2 | 0.85 [0.63–1.14] | 2.93 × 10−1 |
cg10165008 | 13933098 | 0.60 [0.42–0.86] | 6.25 × 10−3 | 0.72 [0.54–0.96] | 2.83 × 10−2 | 0.83 [0.57–1.21] | 3.45 × 10−1 | 0.83 [0.61–1.12] | 2.40 × 10−1 |
cg00040427 | 13933384 | 0.43 [0.29–0.62] | 6.00 × 10−6 | 0.59 [0.44–0.79] | 4.20 × 10−4 | 0.71 [0.48–1.06] | 1.01 × 10−1 | 0.79 [0.58–1.08] | 1.54 × 10−1 |
cg15092231 | 13935853 | 0.49 [0.34–0.71] | 1.49 × 10−4 | 0.65 [0.49–0.87] | 3.66 × 10−3 | 0.79 [0.53–1.18] | 2.62 × 10−1 | 0.87 [0.64–1.18] | 3.82 × 10−1 |
cg07425555 | 13938206 | 0.32 [0.22–0.46] | 3.40 × 10−9 | 0.47 [0.35–0.63] | 5.45 × 10−7 | 0.44 [0.29–0.67] | 1.39 × 10−4 | 0.62 [0.46–0.85] | 3.53 × 10−3 |
cg19921355 | 13938280 | 0.37 [0.25–0.54] | 2.29 × 10−7 | 0.56 [0.42–0.74] | 8.30 × 10−5 | 0.54 [0.35–0.84] | 5.70 × 10−3 | 0.76 [0.55–1.05] | 1.03 × 10−1 |
cg24354933 | 13938482 | 0.33 [0.22–0.49] | 1.95 × 10−8 | 0.51 [0.38–0.68] | 7.00 × 10−6 | 0.55 [0.36–0.84] | 5.93 × 10−3 | 0.72 [0.53–0.99] | 4.74 × 10−2 |
cg11802027 | 13938630 | 0.35 [0.24–0.51] | 5.62 × 10−8 | 0.53 [0.39–0.70] | 1.70 × 10−5 | 0.50 [0.32–0.79] | 3.32 × 10−3 | 0.76 [0.54–1.07] | 1.25 × 10−1 |
cg18547299 | 13938766 | 0.44 [0.30–0.64] | 1.80 × 10−5 | 0.52 [0.39–0.70] | 1.50 × 10−5 | 0.58 [0.38–0.87] | 9.25 × 10−3 | 0.64 [0.47–0.88] | 6.52 × 10−3 |
cg10729062 | 13939010 | 0.48 [0.33–0.69] | 1.05 × 10−4 | 0.50 [0.37–0.67] | 5.00 × 10−6 | 0.73 [0.48–1.10] | 1.37 × 10−1 | 0.73 [0.53–1.01] | 5.73 × 10−2 |
cg11453058 | 13953364 | 0.62 [0.44–0.89] | 1.02 × 10−2 | 0.70 [0.53–0.94] | 1.73 × 10−2 | 0.66 [0.45–0.96] | 3.03 × 10−2 | 0.79 [0.59–1.06] | 1.18 × 10−1 |
cg26969888 | 13953442 | 0.34 [0.24–0.50] | 3.59 × 10−8 | 0.51 [0.38–0.68] | 7.00 × 10−6 | 0.56 [0.38–0.84] | 4.85 × 10−3 | 0.70 [0.51–0.96] | 2.65 × 10−2 |
cg10760452 | 13953776 | 0.72 [0.50–1.02] | 7.00 × 10−2 | 0.83 [0.62–1.10] | 2.07 × 10−1 | 0.79 [0.55–1.13] | 2.06 ×10−1 | 0.94 [0.71–1.27] | 7.26 × 10−1 |
cg10609371 | 13954060 | 0.94 [0.66–1.34] | 7.38 × 10−1 | 1.04 [0.78–1.39] | 7.50 × 10−1 | 1.14 [0.79–1.65] | 4.60 × 10−1 | 1.14 [0.85–1.52] | 3.68 × 10−1 |
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Noor, H.; Zaman, A.; Teo, C.; Sughrue, M.E. PODNL1 Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma. Int. J. Mol. Sci. 2021, 22, 12572. https://doi.org/10.3390/ijms222212572
Noor H, Zaman A, Teo C, Sughrue ME. PODNL1 Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma. International Journal of Molecular Sciences. 2021; 22(22):12572. https://doi.org/10.3390/ijms222212572
Chicago/Turabian StyleNoor, Humaira, Ashraf Zaman, Charles Teo, and Michael E. Sughrue. 2021. "PODNL1 Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma" International Journal of Molecular Sciences 22, no. 22: 12572. https://doi.org/10.3390/ijms222212572
APA StyleNoor, H., Zaman, A., Teo, C., & Sughrue, M. E. (2021). PODNL1 Methylation Serves as a Prognostic Biomarker and Associates with Immune Cell Infiltration and Immune Checkpoint Blockade Response in Lower-Grade Glioma. International Journal of Molecular Sciences, 22(22), 12572. https://doi.org/10.3390/ijms222212572