Background
Materials and methods
Samples
Genomic data and analysis
Determination of aUPD
Statistical analysis
Results
Frequency and distribution of genome-wide aUPD in ovarian cancer
Recurrent aUPD regions and association with OS time and RFS time
Variable
|
OS
| |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Sample set A
|
Sample set B
|
All samples
| ||||||||||
HR
|
95% CI
|
p
|
q
|
HR
|
95% CI
|
p
|
q
|
HR
|
95% CI
|
p
|
q
| |
Age >50 vs <50 | 1.36 | 0.87-2.12 | 0.18 | 0.52 | 1.62 | 1.05-2.52 |
0.031
| 0.14 | 1.50 | 1.09-2.04 |
0.011
| 0.058 |
Stage, I&II vs III&IV | 0.89 | 0.33-2.41 | 0.82 | 0.89 | 5.80 | 2.14-15.70 |
0.0005
|
0.007
| 3.15 | 1.56-6.37 |
0.001
|
0.010
|
Grade, 1&2 vs 3&4 | 1.49 | 0.80-2.79 | 0.21 | 0.52 | 1.50 | 0.96-2.33 | 0.073 | 0.21 | 1.48 | 1.04-2.12 |
0.032
| 0.097 |
Platinum status, | ||||||||||||
Resistance vs sensitive
| 5.28 | 3.23-8.64 |
3.41×10
−11
|
1.26×10
−9
| 3.29 | 2.07-5.22 |
4.28×10
−7
|
1.58×10
−5
| 4.02 | 2.90-5.57 |
2×10
−16
|
2×10
−16
|
Organ side, | ||||||||||||
Bilateral vs unilateral | 1.39 | 0.93-2.1 | 0.11 | 0.45 | 0.98 | 0.67-1.45 | 0.92 | 0.92 | 1.15 | 0.87-1.53 | 0.32 | 0.44 |
aUPD regions | ||||||||||||
17q A
| 1.73 | 1.16-2.58 |
0.007
| 0.06 | 1.67 | 1.17-2.39 |
0.005
|
0.03
| 1.69 | 1.30-2.20 |
0.0001
|
0.0009
|
17q B | 1.40 | 0.94-2.09 | 0.099 | 0.45 | 1.39 | 0.96-2.01 | 0.080 | 0.21 | 1.39 | 1.06-1.81 |
0.017
| 0.07 |
17q C
| 1.51 | 1.02-2.23 |
0.042
| 0.31 | 1.44 | 1.00-2.07 | 0.051 | 0.19 | 1.46 | 1.12-1.90 |
0.005
|
0.03
|
17q D | 1.25 | 0.89-1.77 | 0.202 | 0.52 | 1.38 | 0.99-1.92 | 0.059 | 0.20 | 1.32 | 1.04-1.68 |
0.021
| 0.08 |
17q E | 1.17 | 0.83-1.65 | 0.365 | 0.70 | 1.40 | 1.01-1.96 |
0.046
| 0.19 | 1.29 | 1.01-1.63 |
0.039
| 0.10 |
22q D | 1.43 | 0.75-2.74 | 0.280 | 0.65 | 2.23 | 1.09-4.60 |
0.029
| 0.14 | 1.68 | 1.04-2.71 |
0.035
| 0.10 |
aUPD regions | ||||||||||||
PTEN
| 1.66 | 0.98-2.80 | 0.059 | 0.37 | 1.51 | 0.83-2.73 | 0.175 | 0.34 | 1.56 | 1.06-2.32 |
0.025
| 0.08 |
NF1
| 1.44 | 0.96-2.16 | 0.074 | 0.39 | 1.40 | 0.94-2.07 | 0.094 | 0.22 | 1.43 | 1.08-1.89 |
0.012
| 0.06 |
Whole chromosome
| ||||||||||||
aUPD | 1.80 | 1.23-2.65 |
0.003
|
0.03
| 1.89 | 1.27-2.81 |
0.002
|
0.01
| 1.83 | 1.39-2.41 |
1.59×10
−5
|
0.0002
|
RFS
| ||||||||||||
Age >50 vs <50 | 1.25 | 0.83-1.88 | 0.283 | 0.62 | 1.57 | 1.03-2.38 |
0.037
| 0.11 | 1.39 | 1.04-1.87 |
0.026
| 0.08 |
Stage, I&II vs III&IV | 0.48 | 0.18-1.31 | 0.151 | 0.54 | 2.58 | 1.39-4.79 |
0.003
|
0.02
| 1.85 | 1.10-3.11 |
0.021
| 0.07 |
Grade, 1&2 vs 3&4 | 2.26 | 1.10-4.63 | 0.026 | 0.49 | 1.10 | 0.73-1.66 | 0.639 | 0.81 | 1.34 | 0.95-1.90 | 0.093 | 0.23 |
Platinum status, | ||||||||||||
Resistance vs sensitive
| 2.63 | 1.75-3.95 |
3.15×10
−6
|
0.0001
| 9.04 | 5.76-14.17 |
2×10
−16
|
2×10
−16
| 3.84 | 2.88-5.13 |
2×10
−16
|
2×10
−16
|
Organ side | ||||||||||||
Bilateral vs unilateral | 1.27 | 0.85-1.91 | 0.245 | 0.61 | 1.36 | 0.90-2.05 | 0.148 | 0.39 | 1.30 | 0.97-1.73 | 0.076 | 0.20 |
aUPD regions | ||||||||||||
17q A
| 1.26 | 0.84-1.90 | 0.263 | 0.61 | 1.68 | 1.15-2.44 |
0.007
|
0.03
| 1.47 | 1.11-1.93 |
0.007
|
0.03
|
17q B | 1.60 | 0.77-1.75 | 0.482 | 0.78 | 1.73 | 1.18-2.52 |
0.005
|
0.02
| 1.41 | 1.07-1.87 |
0.014
| 0.06 |
17q C | 1.14 | 0.75-1.72 | 0.535 | 0.78 | 1.73 | 1.18-2.52 |
0.005
|
0.02
| 1.41 | 1.06-1.86 |
0.016
| 0.06 |
17q D
| 1.34 | 0.95-1.89 | 0.098 | 0.54 | 1.55 | 1.11-2.17 |
0.010
|
0.04
| 1.45 | 1.14-1.84 |
0.003
|
0.02
|
17q E
| 1.33 | 0.94-1.88 | 0.106 | 0.54 | 1.77 | 1.26-2.49 |
0.0009
|
0.01
| 1.54 | 1.21-1.96 |
0.0005
|
0.008
|
17q F
| 1.28 | 0.91-1.81 | 0.162 | 0.54 | 1.68 | 1.20-2.36 |
0.002
|
0.02
| 1.47 | 1.16-1.87 |
0.002
|
0.02
|
17q G
| 1.30 | 0.92-1.85 | 0.135 | 0.54 | 1.70 | 1.21-2.38 |
0.002
|
0.02
| 1.49 | 1.17-1.89 |
0.001
|
0.01
|
17q H | 1.37 | 0.94-1.99 | 0.102 | 0.54 | 1.22 | 0.87-1.71 | 0.245 | 0.49 | 1.29 | 1.00-1.66 |
0.044
| 0.13 |
aUPD regions | ||||||||||||
PTEN
| 1.10 | 0.61-1.54 | 0.761 | 0.88 | 1.32 | 0.67-2.61 | 0.419 | 0.57 | 1.17 | 0.75-1.83 | 0.495 | 0.72 |
NF1
| 1.23 | 0.81-1.87 | 0.341 | 0.66 | 1.64 | 1.11-2.44 |
0.013
|
0.05
| 1.42 | 1.07-1.89 |
0.017
| 0.06 |
BRCA1
| 1.13 | 0.76-1.67 | 0.548 | 0.78 | 1.97 | 1.36-2.84 |
0.0003
|
0.006
| 1.49 | 1.14-1.94 |
0.003
|
0.02
|
Whole chromosome | ||||||||||||
aUPD | 1.16 | 0.77-1.75 | 0.473 | 0.77 | 1.22 | 0.78-1.89 | .379 | 0.57 | 1.18 | 0.88-1.59 | 0.275 | 0.64 |
Variable
|
HR
|
95% CI
|
p
|
---|---|---|---|
OS (all samples)
| |||
Platinum status, | |||
Resistance vs sensitive | 3.27 | 2.09-5.12 | 2.37×10−7
|
aUPD at | |||
whole-chromosome | 1.82 | 1.15-2.88 | 0.0108 |
OS (sample set A)
| |||
Platinum status, | |||
Resistance vs sensitive | 5.14 | 2.81-9.4 | 1.01×10−7
|
aUPD at | |||
whole chromosome | 2.17 | 1.29-3.66 | 0.0036 |
OS (sample set B)
| |||
Platinum status, | |||
Resistance vs sensitive | 2.48 | 1.12-5.47 | 0.0246 |
RFS (all samples)
| |||
Platinum status, | |||
Resistance vs sensitive | 4.16 | 3.07-5.64 | 2×10−16
|
RFS (sample set A)
| |||
Platinum status | |||
Resistance vs sensitive | 2.93 | 2.00-4.30 | 3.24×10−8
|
RFS (sample set B)
| |||
Platinum status, | |||
Resistance vs sensitive | 58.42 | 19.22-171.29 | 1.25×10−13
|
Additional associations with aUPD regions
Chromosomal region
|
Chromosomal position
|
Start-end position
|
Genes
|
---|---|---|---|
17q A | 17q12-q21.2 | 35.139.198-35.611.217 |
GRB7
,
IKZF3
,
ZPBP2
,
GSDMB
, ORMDL3, LRRC3C, GSDMA,
PSMD3, CSF3
,
MED24, THRA
, NR1D1, MSL1,
CASC3
,
RAPGEFL1
|
17q B | 17q21.2 | 37.079.721-37.604.187 |
EIF1,
HAP1
, GAST,
JUP
, LEPREL4, NT5C3L,
FKBP10
,
KLHL10
, KLHL11,
ACLY
,
TTC25
, CNP,
DNAJC7, NKIRAS2
, ZNF385C, DHX58,
KAT2A
, HSPB9, RAB5C, KCNH4, HCRT, GHDC
|
17q C | 17q21.2 | 37.244.697-37.559.796 |
NT5C3L,
FKBP10
,
KLHL10,
KLHL11
,
ACLY, TTC25
, CNP,
DNAJC7, NKIRAS2
, ZNF385C, DHX58,
KAT2A
, HSPB9, RAB5C
|
17q D | 17q21.33 | 45.311.230-45.815.839 |
DLX4, DLX3, LOC284080, ITGA3, PDK2, PPP1R9B,
SGCA
, HILS1,
COL1A1
, TMEM92, XYLT2, MRPL27,
EME1
, LRRC59
|
17q E | 17q22 | 48.041.053-43.303.286 | No gene |
17q F | 17q22 | 49.352.217-49.666.897 | No gene |
17q G | 17q22 | 49.771.790-50.243.809 | No gene |
22q B | 22q11.2 | 29.263.787-29.738.848 |
SEC14L6, GAL3ST1, PES1,
SLC35E4
, TCN2, DUSP18,
OSBP2
,
MORC2
, TUG1
|