Background
Methods
Patients and samples
Immunohistochemistry
Cells and transfection
Assay of gene expression by real-time RT-PCR
Western blot analysis
In vitro cell viability
Colony formation assay
Cell cycle and cell apoptosis analyses
ChIP-qPCR and ChIP-Seq
Animal studies
Statistical analysis
Results
DOT1L and H3K79 methylation expression in normal ovarian tissues and benign, borderline, and malignant ovarian tumors
Association between DOT1L expression and clinicopathological parameters of OC
Characteristics | Sample | DOT1L expression |
χ
2
|
P
| |
---|---|---|---|---|---|
Low expression | High expression | ||||
Age at diagnosis | 235 | 0.120 | 0.729 | ||
≤50 | 114 | 51 (44.7%) | 63 (55.3%) | ||
>50 | 117 | 55 (47.0%) | 62 (53.0%) | ||
Unknown | 4 | ||||
FIGO stage | 235 | 17.655 | 0.001 | ||
I | 20 | 18 (90.0%) | 2 (10.0%) | ||
II | 17 | 8 (47.1%) | 9 (52.9%) | ||
III | 159 | 66 (41.5%) | 93 (58.5%) | ||
IV | 29 | 11 (37.9%) | 18 (62.1%) | ||
Unknown | 10 | ||||
Histologic grade | 235 | 8.831 | 0.012 | ||
Grade 1 | 40 | 27 (67.5%) | 13 (32.5%) | ||
Grade 2 | 58 | 24 (41.4%) | 34 (58.6%) | ||
Grade 3 | 120 | 50 (41.7%) | 70 (58.3%) | ||
Unknown | 17 | ||||
Ascites | 235 | 0.005 | 0.944 | ||
Yes | 173 | 78 (45.1%) | 95 (54.9%) | ||
No | 36 | 16 (44.4%) | 20 (55.6%) | ||
Unknown | 26 | ||||
LN metastasis | 235 | 4.392 | 0.036 | ||
Yes | 73 | 29 (39.7%) | 44 (60.3%) | ||
No | 106 | 59 (55.7%) | 47 (44.3%) | ||
Unknown | 56 | ||||
Preoperative CA125 (U/ml) | 235 | 1.829 | 0.176 | ||
≤600 | 68 | 33 (48.5%) | 35 (51.5%) | ||
>600 | 80 | 30 (37.5%) | 50 (62.5%) | ||
Unknown | 87 |
High expression of DOT1L as an independent prognostic marker of OC
Overall survival | Progression free survival | |||||
---|---|---|---|---|---|---|
HR | 95% CI |
P
| HR | 95% CI |
P
| |
FIGO stage (early stage vs. advanced stage) | 1.127 | 0.357–3.562 | 0.838 | 1.744 | 0.576–5.288 | 0.325 |
Histologic grade (well vs. poor and moderate) | 0.615 | 0.256–1.475 | 0.276 | 0.904 | 0.393–2.077 | 0.811 |
Ascites (no vs. yes) | 0.850 | 0.381–1.897 | 0.692 | 0.667 | 0.337–1.323 | 0.247 |
LN metastasis (no vs. yes) | 0.924 | 0.460–1.856 | 0.823 | 0.786 | 0.410–1.506 | 0.468 |
Age (≤50 vs. >50 years) | 2.920 | 1.466–5.815 | 0.002 | 2.403 | 1.302–4.435 | 0.005 |
Preoperative CA125 (U/ml) (≤600 vs. >600) | 0.548 | 0.280–1.073 | 0.079 | 0.327 | 0.177–0.607 | 0.000 |
DOT1L expression (low vs. high) | 4.705 | 2.160–10.248 | 0.000 | 8.884 | 3.974–19.861 | 0.000 |