GLIS1, Correlated with Immune Infiltrates, Is a Potential Prognostic Biomarker in Prostate Cancer
Abstract
:1. Introduction
2. Results
2.1. Identification of tDEGs, tDEMs and tDEM-TGs in Prostate Cancer
2.2. GO and Pathway Enrichment Analysis
2.3. Identification of Key Genes and miRNAs
2.4. Diagnostic and Prognostic Values of GLIS1 in Pan-Cancer
2.5. GLIS1 Was Associated with the Prognosis of Prostate Cancer Patients
2.6. Functional Enrichment and Pathway Analysis of High and Low-GLIS1 Expression Samples
2.7. The Correlation between GLIS1 Expression and Immune Infiltration Levels
2.8. The Association between GLIS1, Chemokines and Chemokine Receptors
3. Discussion
4. Materials and Methods
4.1. GEO Data Extraction and DEGs/DEMs/tDEGs/tDEMs Analysis
4.2. Enrichment Analysis and Key Genes Acquisition
4.3. Expression and Prognosis of GLIS1 in Pan-Cancer
4.4. Analysis of DEGs between the High and Low GLIS1 Expression Groups in PRAD Patients
4.5. Gene Set Enrichment Analysis (GSEA)
4.6. Immune Infiltration in Tumor Tissues
4.7. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Gene | Datasets | LogFC | p Value | adj. p Value | Expression |
---|---|---|---|---|---|
GLIS1 | GSE183019 | −0.63 | 0.000 | 0.012 | DOWN |
GSE134073 | −2.09 | 0.000 | 0.000 | DOWN | |
GSE69223 | −0.94 | 0.002 | 0.017 | DOWN | |
GSE88808 | −0.77 | 0.000 | 0.000 | DOWN |
Target Gene | miRNA | Datasets | LogFC | p Value | adj. p Value | Expression |
---|---|---|---|---|---|---|
GLIS1 | hsa-miR-663b | GSE60117 | 0.28 | 0.000 | 0.000 | UP |
GSE89193 | 1.36 | 0.000 | 0.000 | UP | ||
GLIS1 | hsa-miR-153 | GSE60117 | 0.35 | 0.003 | 0.015 | UP |
GSE89193 | 2.22 | 0.000 | 0.000 | UP | ||
GLIS1 | hsa-miR-483-5p | GSE60117 | −0.62 | -0.010 | 0.039 | DOWN |
GSE89193 | −1.10 | 0.001 | 0.006 | DOWN |
Clinicopathologic Variables | No. of Cases | GLIS1 Expression Level | χ | p | |
---|---|---|---|---|---|
Low | High | ||||
All cases | 499 | 249(44.3%) | 250(55.7%) | ||
Age | 0.019 | 0.889 | |||
≤60 | 224 (44.9%) | 111 (22.2%) | 113 (22.6%) | ||
>60 | 275 (55.1%) | 138 (27.7%) | 137 (27.5%) | ||
Clinical T stage | 0.623 | 0.430 | |||
T1 + T2 | 351 (86.5%) | 165 (40.6%) | 186 (45.8%) | ||
T3 + T4 | 55 (13.5%) | 29 (7.1%) | 26 (6.4%) | ||
Pathologic T stage | 8.256 | 0.004 | |||
T2 | 189 (38.4%) | 79 (16.1%) | 110 (22.4%) | ||
T3 + T4 | 303 (61.6%) | 167 (33.9%) | 136 (27.6%) | ||
Lymph nodes status | 6.477 | 0.011 | |||
Negative | 347 (81.5%) | 169 (39.7%) | 178 (41.8%) | ||
Positive | 79 (18.5%) | 51 (12.0%) | 28 (6.6%) | ||
PSA (ng/mL) | 7.179 | 0.007 | |||
<4 | 415 (93.9%) | 197 (44.6%) | 218 (49.3%) | ||
≥4 | 27 (6.1%) | 20 (4.5%) | 7 (1.6%) | ||
Gleason score | 6.674 | 0.010 | |||
6–7 | 293 (58.7%) | 132 (26.5%) | 161 (32.3%) | ||
8–10 | 206 (41.3%) | 117 (23.4%) | 89 (17.8%) | ||
Survival Status | 6.564 | 0.010 | |||
Live | 489 (98.0%) | 240 (48.1%) | 249 (49.9%) | ||
Dead | 10 (2.0%) | 9 (1.8%) | 1 (0.2%) |
Characteristics | Total (N) | Univariate Analysis | Multivariate Analysis | ||
---|---|---|---|---|---|
Hazard Ratio (95% CI) | p Value | Hazard Ratio (95% CI) | p Value | ||
Age | 499 | ||||
≤60 | 224 | Reference | |||
>60 | 275 | 1.577 (0.440–5.648) | 0.484 | ||
T stage | 492 | ||||
T2 | 189 | Reference | |||
T3 & T4 | 303 | 3.294 (0.612–17.727) | 0.165 | ||
N stage | 426 | ||||
N0 | 347 | Reference | |||
N1 | 79 | 3.516 (0.778–15.896) | 0.102 | ||
PSA (ng/mL) | 442 | ||||
<4 | 415 | Reference | |||
≥4 | 27 | 10.479 (2.471–44.437) | 0.001 | 3.411 (0.735–15.826) | 0.117 |
Gleason score | 499 | ||||
6 & 7 | 293 | Reference | |||
8 & 9 & 10 | 206 | 6.664 (1.373–32.340) | 0.019 | 5.372 (0.843–34.209) | 0.075 |
Residual tumor | 468 | ||||
R0 | 315 | Reference | |||
R1 & R2 | 153 | 2.598 (0.696–9.694) | 0.155 | ||
GLIS1 | 499 | ||||
Low | 249 | Reference | |||
High | 250 | 0.122 (0.015–0.965) | 0.046 | 0.157 (0.018–1.355) | 0.092 |
Characteristics | Total (N) | Odds Ratio (OR) | p Value |
---|---|---|---|
Age (>60 vs. ≤60) | 499 | 1.007 (0.708–1.434) | 0.968 |
T stage (T3 & T4 vs. T2) | 492 | 0.585 (0.404–0.843) | 0.004 |
N stage (N1 vs. N0) | 426 | 0.521 (0.311–0.859) | 0.012 |
PSA (ng/mL) (≥4 vs. <4) | 442 | 0.316 (0.122–0.731) | 0.011 |
Gleason score (8 & 9 & 10 vs. 6 & 7) | 499 | 0.645 (0.450–0.922) | 0.017 |
Race (Black or African American & White vs. Asian) | 484 | 3.130 (0.921–14.237) | 0.090 |
Residual tumor (R1 & R2 vs. R0) | 468 | 0.671 (0.454–0.990) | 0.045 |
Gene Markers | PRAD | ||||
---|---|---|---|---|---|
None | Purity | ||||
Correlation | p | Correlation | p | ||
CD8+ T cell | CD8A | 0.423 | 4.54 × 10−23 | 0.238 | 9.38 × 10−7 |
CD8B | 0.275 | 4.27 × 10−10 | 0.158 | 1.24 × 10−3 | |
T cell (general) | CD3D | 0.329 | 4.71 × 10−14 | 0.115 | 1.91 × 10−2 |
CD3E | 0.405 | 4.8 × 10−21 | 0.203 | 2.98 × 10−5 | |
CD2 | 0.366 | 2.94 × 10−17 | 0.181 | 2.15 × 10−4 | |
B cell | CD19 | 0.247 | 2.42 × 10−8 | 0.11 | 2.45 × 10−2 |
CD79A | 0.221 | 6.67 × 10−7 | 0.077 | 1.18 × 10−1 | |
Monocyte | CD86 | 0.284 | 1.00 × 10−10 | 0.131 | 7.67 × 10−3 |
CD115 (CSF1R) | 0.481 | 3.08 × 10−30 | 0.344 | 5.46 × 10−13 | |
TAM | CCL2 | 0.302 | 5.37 × 10−12 | 0.149 | 2.38 × 10−3 |
CD68 | −0.311 | 7.92 × 10−11 | 0.08 | 1.04 × 10−1 | |
IL10 | 0.29 | 4.42 × 10−11 | 0.188 | 1.17 × 10−4 | |
M1 macrophage | INOS (NOS2) | 0.29 | 4.42 × 10−11 | 0.188 | 1.17 × 10−4 |
IRF5 | 0.133 | 2.95 × 10−3 | 0.064 | 1.91 × 10−1 | |
COX2 (PTGS2) | 0.353 | 4.81 × 10−16 | 0.254 | 1.46 × 10−7 | |
M2 macrophage | CD163 | 0.185 | 3.15 × 10−5 | 0.061 | 2.15 × 10−1 |
VSIG4 | 0.29 | 4.12 × 10−11 | 0.159 | 1.18 × 10−3 | |
MS4A4A | 0.224 | 4.57 × 10−7 | 0.082 | 9.54 × 10−2 | |
Neutrophils | CD66b (CEACAM8) | 0.038 | 3.99 × 10−1 | 0.007 | 8.79 × 10−1 |
CD11B (ITGAM) | 0.387 | 3.08 × 10−19 | 0.241 | 6.59 × 10−7 | |
CCR7 | 0.306 | 2.97 × 10−12 | 0.089 | 7.11 × 10−2 | |
Natural killer cell | KIR2DL1 | 0.046 | 3.02 × 10−1 | −0.048 | 3.25 × 10−1 |
KIR2DL3 | 0.118 | 8.44 × 10−3 | 0.115 | 1.89 × 10−2 | |
KIR2DL4 | 0.116 | 9.66 × 10−3 | 0.007 | 8.82 × 10−1 | |
KIR3DL1 | 0.101 | 2.44 × 10−2 | −0.006 | 8.96 × 10−1 | |
KIR3DL2 | 0.094 | 3.54 × 10−2 | 0.055 | 2.65 × 10−1 | |
KIR3DL3 | 0.004 | 9.35 × 10−1 | 0.063 | 1.99 × 10−1 | |
KIR2DS4 | 0.148 | 9.07 × 10−4 | 0.092 | 5.98 × 10−2 | |
Dendritic cell | HLA-DPB1 | 0.49 | 1.75 × 10−31 | 0.326 | 9.84 × 10−12 |
HLA-DQB1 | 0.264 | 2.08 × 10−9 | 0.132 | 6.87 × 10−3 | |
HLA-DRA | 0.351 | 7.66 × 10−16 | 0.161 | 1.00 × 10−3 | |
HLA-DPA1 | 0.423 | 4.35 × 10−23 | 0.271 | 1.93 × 10−8 | |
BDCA-1 (CD1C) | 0.442 | 3.4 × 10−25 | 0.268 | 2.70 × 10−8 | |
BDCA-4 (NRP1) | −0.004 | 9.27 × 10−1 | −0.023 | 6.44 × 10−1 | |
CD11c (ITGAX) | 0.244 | 3.67 × 10−8 | 0.087 | 7.61 × 10−2 | |
Th1 | T-bet (TBX21) | 0.332 | 2.9 × 10−14 | 0.154 | 1.63 × 10−3 |
STAT4 | 0.354 | 3.94 × 10−16 | 0.178 | 2.56 × 10−4 | |
STAT1 | 0.087 | 5.35 × 10−2 | −0.01 | 8.43 × 10−1 | |
IFN-γ (IFNG) | 0.091 | 4.19 × 10−2 | −0.002 | 9.75 × 10−1 | |
TNF-α (TNF) | 0.214 | 1.52 × 10−6 | 0.096 | 4.92 × 10−2 | |
Th2 | GATA3 | 0.643 | 1.62 × 10−59 | 0.545 | 1.33 × 10−33 |
STAT6 | 0.437 | 1.13 × 10−24 | 0.356 | 7.61 × 10−14 | |
STAT5A | 0.622 | 1.33 × 10−54 | 0.499 | 1.30 × 10−27 | |
IL13 | 0.058 | 1.95 × 10−1 | 0.014 | 7.79 × 10−1 | |
Tfh | BCL6 | 0.288 | 6.22 × 10−11 | 0.146 | 2.90 × 10−3 |
IL21 | 0.053 | 2.39 × 10−1 | 0.008 | 8.73 × 10−1 | |
Th17 | STAT3 | 0.255 | 7.41 × 10−9 | 0.148 | 2.53 × 10−3 |
IL17A | 0.159 | 3.56 × 10−4 | 0.023 | 6.47 × 10−1 | |
Treg | FOXP3 | 0.188 | 2.41 × 10−5 | 0.075 | 1.27 × 10−1 |
CCR8 | 0.125 | 5.06 × 10−3 | 0.025 | 6.11 × 10−1 | |
STAT5B | 0.5 | 6.45 × 10−33 | 0.432 | 2.33 × 10−20 | |
TGF-β (TGFB1) | 0.532 | 1.08 × 10−37 | 0.412 | 1.94 × 10−18 | |
T cell exhaustion | PD-1 (PDCD1) | 0.317 | 4.27 × 10−13 | 0.128 | 8.92 × 10−3 |
CTLA4 | 0.146 | 1.08 × 10−3 | −0.025 | 6.17 × 10−1 | |
TIM-3 (HAVCR2) | 0.275 | 4.25 × 10−10 | 0.122 | 1.30 × 10−2 | |
GZMB | 0.222 | 5.57 × 10−7 | 0.023 | 6.37 × 10−1 | |
LAG3 | 0.466 | 3.62 × 10−28 | 0.346 | 3.67 × 10−13 | |
PDL1 (CD274) | 0.286 | 7.63 × 10−11 | 0.158 | 1.23× 10−3 |
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Peng, Q.; Xie, T.; Wang, Y.; Ho, V.W.-S.; Teoh, J.Y.-C.; Chiu, P.K.-F.; Ng, C.-F. GLIS1, Correlated with Immune Infiltrates, Is a Potential Prognostic Biomarker in Prostate Cancer. Int. J. Mol. Sci. 2024, 25, 489. https://doi.org/10.3390/ijms25010489
Peng Q, Xie T, Wang Y, Ho VW-S, Teoh JY-C, Chiu PK-F, Ng C-F. GLIS1, Correlated with Immune Infiltrates, Is a Potential Prognostic Biomarker in Prostate Cancer. International Journal of Molecular Sciences. 2024; 25(1):489. https://doi.org/10.3390/ijms25010489
Chicago/Turabian StylePeng, Qiang, Tingting Xie, Yuliang Wang, Vincy Wing-Sze Ho, Jeremy Yuen-Chun Teoh, Peter Ka-Fung Chiu, and Chi-Fai Ng. 2024. "GLIS1, Correlated with Immune Infiltrates, Is a Potential Prognostic Biomarker in Prostate Cancer" International Journal of Molecular Sciences 25, no. 1: 489. https://doi.org/10.3390/ijms25010489
APA StylePeng, Q., Xie, T., Wang, Y., Ho, V. W.-S., Teoh, J. Y.-C., Chiu, P. K.-F., & Ng, C.-F. (2024). GLIS1, Correlated with Immune Infiltrates, Is a Potential Prognostic Biomarker in Prostate Cancer. International Journal of Molecular Sciences, 25(1), 489. https://doi.org/10.3390/ijms25010489