High ΔNp73/TAp73 ratio is associated with poor prognosis in acute
promyelocyticleukemia
Supplementary Data
GeneexpressionprofileofTP73isoforms:FollowingtotalRNAextraction,
real‐time quantitative polymerase chain reaction (RQ‐PCR) assays with sample‐
derived cDNA were performed in duplicate on MicroAmp optical 96‐well plates
using a 7500 Real‐Time PCR System (Applied BioSystems, Foster City, CA, USA)
with the ABL FusionQuant Standard Kit as endogenous control. The expression
levels of TP73 isoforms were quantified using TaqMan Gene Expression Assay
(Applied BioSystems, Foster City, CA, USA), following the manufacturer’s
instructions.Briefly,RQ‐PCRassayswereperformedinafinalreactionvolumeof
20µL,containing10µLof2×TaqManUniversalPCRMasterMix,200ngcDNA,and
lµLof20×forwardandreverseprimersandprobes.Eachspecificprobe(capable
ofdifferentiatingthetranscriptionallyinactiveandactiveisoformsofTP73gene)
(ΔNp73, Assay ID: Hs01065727_m1; TAp73, Assay ID: Hs00232088_m1) was
labeled with FAM dye and with non‐fluorescent quencher. Amplification was
carriedoutat50°Cfor2minutesand95°Cfor10minutes,followedby40cyclesof
95°Cfor15secondsand60°Cfor1minute.Incaseofadiscrepancygreaterthan1
in cycle of threshold (Ct) values between duplicates, a third test was performed.
ThecomparativeCtmethodwasusedtodeterminetherelativeexpressionlevelof
ΔNp73andTAp73.ThedifferenceinCtnumber(ΔCt=CtΔNp73 or TAp73 –CtABL)was
calculated for each replicate. Without detectable gene amplification within 40
cycles,therespectivegeneexpressionvaluesweresetat0.
The gene expression of ΔNp73 and TAp73 was calculated relative to a
reference cDNA (NB4 cell line, a human acute promyelocytic leukemia cell line,
positive for PML/RARA fusion gene) and set at 1. Of importance, the same
reference cDNA was used as an internal control throughout all experiments to
ensure that the results would be fully comparable among experiments. The gene
expressionvaluesofΔNp73andTAp73werecalculatedasrelativequantification
(RQ) = 2‐ΔΔCt and ΔΔCt = ΔCtpatients – ΔCtNB4 cell line. The results are expressed as a
ratio between truncated ΔNp73 and full‐length TAp73 isoforms, and hereinafter
calledΔNp73/TAp73ratio.
Western blotting and antibodies: Whole‐cell lysates were prepared as
previously described.1 Mouse anti‐β‐actin (sc‐81178) was purchased from Santa
CruzBiotechnology(SantaCruz,CA,USA)andhorseradishperoxidase‐conjugated
secondary antibody horse anti‐mouse IgG (#7076) was purchased from Cell
Signaling (Beverly, MA, USA). Anti‐TAp73 (IMG‐246) and anti‐ΔNp73 (IMG‐313)
antibodieswereused(Imgenex,SanDiego,CA).Theantibody‐proteincomplexwas
detectedusingtheECLWesternBlottingDetectionReagents(GELifesciences).
Statistical analysis and clinical endpoints: Patient baseline characteristics
werereporteddescriptively.Fisher’sexacttestorChi‐squaretest,asappropriate,
wasusedtocomparecategoricalvariables,andWilcoxonrank‐sumtestwasused
to compare continuous variables. Correlation analysis was performed using the
Spearman rank test. Using survival ROC analysis2 and C index,3 patients were
dichotomized into two groups according to the ΔNp73/TAp73 ratio (low
expression group, < 1.6; high expression group, ≥ 1.6). Overall survival (OS) and
disease‐free survival (DFS) were calculated using the Kaplan–Meier method. OS
wasdefinedasthetimefromtheinitiationofinductiontherapytodeathfromany
cause;thosealiveorlosttofollow‐upwerecensoredatthedatelastknownalive.
DFS was defined as the time from complete remission to disease relapse,
development of secondary malignancy, or death from any cause, whichever
occurred first. Patients who were alive without disease relapse or secondary
malignancy were censored at the time last seen alive and disease‐free. The
log‐rank test was used for comparisons of Kaplan–Meier curves. Cumulative
incidence curves for non‐relapse death and relapse with or without death were
constructed,reflectingtimetorelapseandtimetonon‐relapsedeathascompeting
risks.4Timetorelapseandtimetonon‐relapsedeathweremeasuredfromthedate
ofcompleteremission.
Univariable and multivariable proportional hazards regression analysis was
performed for potential prognostic factors for OS. Potential prognostic factors
examined in multivariable regression analysis were age at diagnosis, patient sex,
white blood cell (WBC) counts, platelet counts, hemoglobin levels, coagulopathy,
FAB classification, PML breakpoint, coagulopathy, creatinine, albumin, uric acid,
fibrinogen, and bone marrow blasts. Proportional hazards assumption for each
variable of interest was tested. Linearity assumption for all continuous variables
wasexaminedusingrestrictedcubicsplineestimatesoftherelationshipbetween
the continuous variable and log relative hazard/risk. Multivariable regression
analysisforrelapse,non‐relapsedeath,andDFSwasnotperformedbecauseofthe
smallnumberofevents.AllPvaluesweretwosidedwithasignificancelevelof.05.
All calculations were performed using SAS 9.2 (SAS Institute, Cary, NC) and R
2.10.1(TheCRANproject–www.r‐project.org)software.
RESULTS
Supplemental Table 1 shows the summary of primary data for ΔNp73,
TAp73, and the ΔNp73/TAp73 ratio. Supplemental Table 2 shows the crude
primarydata.TherewasastrongcorrelationbetweenΔNp73andΔNp73/TAp73
ratio (r = 0.89) but no correlation between TAp73 and ΔNp73/TAp73 ratio (r =
0.06). In addition, there was a weak correlation between ΔNp73 and TAp73 (r =
0.43). To facilitate the interpretation of the ΔNp73/TAp73 ratio in the clinical
context, we attempted to dichotomize the ΔNp73/TAp73 ratio as low (< 1.6) or
high(≥1.6).
SupplementalTable1.Summaryofprimarydatafor ΔNp73,TAp73, andΔNp73/TAp73
ratio
Gene
N
median(range)
ΔNp73/TAp73
129
0.6(0to72.6)
TAp73
129
23.5(0to316)
ΔNp73
129
11(0to3371)
SupplementalTable2.PrimarydataforAPLpatients.
PONDID
Gender Age
HCFMR‐000018
female
27,5917808 Intermediaterisk
Categoryrisk
bcr3
HCFMR‐000020
male
32,490411
bcr3
HCFMR‐000024
male
20,8191781 Intermediaterisk
HCFMR‐000025
male
15,9780822 Intermediaterisk
HCFMR‐000026
female
53,4630137 Intermediaterisk
HCFMR‐000027
male
36,1315068 Highrisk
HCFMR‐000029
female
24,5260274 Lowrisk
bcr3
M3
0,02383525
HCFMR‐000031
female
41,6356164 Intermediaterisk
bcr3
M3
32,11789725 18,16970196 0,565718914
HCFMR‐000033
male
21,4739726 Lowrisk
bcr1
M3
HCFMR‐000034
female
73,6
bcr1
M3
HCFMR‐000035
female
42,1671233 Intermediaterisk
bcr3
M3
HCFMR‐000037
female
22,7424658 Lowrisk
bcr3
M3
HCPA‐000006
male
44,3369863 Intermediaterisk
bcr3
M3
13,96261093 8,151721098 0,583824984
HCPA‐000007
male
27,2821918 Intermediaterisk
bcr1
M3
38,26582756 24,22231864 0,633001301
HCPA‐000008
female
34,7534247 Intermediaterisk
bcr1
M3
5,218924037 240,7508952 46,13036969
HCPA‐000009
male
31,4575342 Intermediaterisk
bcr1
M3
0,042115353 0,326933716 7,762815504
HCPA‐000010
female
27,7506849 Highrisk
bcr1
M3
40,22162232 487,504387
HCPA‐000011
female
16,8958904 Intermediaterisk
bcr1
M3
73,73852811 0,307288291 0,004167269
HCPA‐000012
male
28,7123288 Highrisk
bcr3
M3
59,67684537 100,4688687 1,683548587
HCPA‐000013
female
9,34246575 Highrisk
bcr3
M3
316,2771686 841,7588674 2,661459476
Intermediaterisk
Lowrisk
PMLbreakpoint FAB
bcr1
bcr3
TAp73
ΔNp73
ΔNp73/TAp73
M3v 18,69796331 0,012644126 0,00067623
M3
M3
0,000256118 1,94719E‐07
0,000760268
M3
32,53441807 23,2740251
0,715366264
M3
51,70417182 30,38841183 0,587736168
M3v 0,026636564 0,206774733 7,762815504
0,001377092 0,057775434
32,11789725 0,02949037
0,000918191
12,12045559
HCPA‐000017
female
36,4164384 Intermediaterisk
bcr1
M3
63,10861065 49,78366104 0,78885687
HCPA‐000018
female
50,8821918 Highrisk
bcr1
M3
64,9234415
HCPA‐000019
male
58,7068493 Intermediaterisk
bcr3
M3
14,42838307 46,74187607 3,239578257
HCPA‐000020
male
33,6438356 Intermediaterisk
bcr1
M3
119,0028389 135,4153365 1,137916858
HCPA‐000022
female
61,7315068 Intermediaterisk
bcr1
M3
49,72072187 47,42623098 0,953852422
HCPA‐000024
female
20,6356164 Highrisk
bcr1
M3
4,362909783 3,892764627 0,892240459
HCPA‐000025
male
38,5780822 Lowrisk
bcr3
M3
6,578474998 2,768587765 0,420855558
139,804264
HCPA‐000026
female
26,9808219 Intermediaterisk
bcr3
M3
14,9969567
HCPA‐000027
male
33,2328767 Highrisk
bcr3
M3
3,771424135 2,801001108 0,742690561
bcr1
M3
31,15823597 0,304942507 0,009786899
bcr3
M3
7,262673944 0,059526999 0,008196292
HCPA‐000028
male
42,2
HCPA‐000029
female
48,0986301 Highrisk
Intermediaterisk
HCPA‐000030
female
32,1260274 Highrisk
47,8256945
2,153371121
3,189026644
M3
HCPA‐000019
male
58,7068493 Intermediaterisk
bcr1
M3
37,487353
0,178326062 0,004756966
HCPA‐000032
male
46,3972603 Highrisk
bcr1
M3
2,229058
0,007250213 0,003252591
HCPA‐000033
male
39,1287671 Highrisk
M3
43,475094
0,072340126 0,001663944
HCPA‐000034
male
26,9890411 Highrisk
bcr3
M3
13,521324
104,9635436 7,762815504
HCPA‐000035
female
45,4684932 Intermediaterisk
bcr1
M3
bcr1
HCPA‐000036
male
21,1506849 Highrisk
HCPA‐000037
female
28,5123288 Highrisk
M3
13,090773
0,061690074 0,004712485
M3
13,195415
1,412352557 0,107033584
0,082262766 0,037567075
HCPA‐000038
female
57,7506849 Intermediaterisk
bcr1
M3
2,189757
HCPR‐000005
male
52,4191781 Intermediaterisk
bcr1
M3
4,978657791 6,993205375 1,404636685
HCPR‐000006
female
26,4876712 Intermediaterisk
bcr1
M3
12,81562594 21,07408907 1,644405757
HCPR‐000007
female
42,9643836 Highrisk
bcr1
M3
62,9535113
258,6955346 4,109310653
HCPR‐000008
female
44,509589
Highrisk
bcr1
M3
4,740371
17,03099334 3,592755365
HCPR‐000009
female
65,4328767 Lowrisk
bcr3
M3
33,56987342 0,001413161 4,20961E‐05
HCPR‐000012
male
51,1945205 Intermediaterisk
bcr1
M3
3,293712654 0,28831455
HCPR‐000013
female
36,1369863 Intermediaterisk
bcr1
M3
48,58168943 34,29838976 0,705994175
0,087534822
HCPR‐000014
male
27,9041096 Highrisk
bcr1
M3
32,13881161 592,06799
HCPR‐000015
male
60,6575342 Highrisk
bcr1
M3
106,070486
18,42221166
HCPR‐000016
male
48,4986301 Highrisk
M3
53,77771025 337,2748857 6,271648311
HCPR‐000017
female
21,8767123 Highrisk
bcr3
M3
34,40683037 51,45764099 1,495564702
HCPR‐000018
male
21,2054795 Highrisk
bcr1
M3
825,4125271 7,781736072
HCPR‐000019
female
22,1123288 Lowrisk
bcr1
M3
72,94150299 51,92705553 0,711899994
HCPR‐000020
female
26,1643836 Highrisk
bcr3
M3
0,023835
0,008173099 0,342903238
HCPR‐000022
male
23,3150685 Highrisk
bcr3
M3
HCPR‐000023
6,372647
0,082348648 0,012922204
male
34,5150685 Lowrisk
bcr1
M3
HEMOP‐000014 male
46,5123288 Highrisk
bcr1
M3v 2,436346024 137,3269835 56,36596039
HEMOP‐000018 male
27,1150685 Intermediaterisk
bcr1
M3
HEMOP‐000021 female
34,9753425 Intermediaterisk
bcr1
M3
13,37855535 33,53761956 2,506819211
HEMOP‐000023 male
26,6821918 Highrisk
bcr3
M3
38,265828
HEMOP‐000026 female
58,3643836 Highrisk
bcr1
M3v 20,45153184 32,13136336 1,571098127
HEMOP‐000029 male
50,2739726 Lowrisk
bcr1
M3
HEMOP‐000032 female
35,9616438 Intermediaterisk
bcr1
M3
Intermediaterisk
M3
44,00504929 42,53645024 0,966626579
756,0212371 19,75708554
35,08673999 11,21643385 0,319677287
HEMOP‐000035 male
48,690411
HEMOP‐000036 female
25,0273973 Lowrisk
bcr2
M3
23,50570118 235,9042144 10,03604243
HEMOP‐000037 male
28,4630137 Lowrisk
bcr1
M3
HEMOP‐000038 female
29,6493151 Lowrisk
HEMOP‐000039 male
46,9068493 Highrisk
bcr3
M3
35,36365718 103,8883958 2,937716403
HEMOP‐000040 female
53,8246575 Lowrisk
bcr3
M3
27,57064095 30,20121954 1,095412312
M3
HEMOP‐000041 female
24,2438356 Highrisk
bcr3
M3
37,37545066 17,60359077 0,470993405
HEMOP‐000042 male
34,0219178 Intermediaterisk
bcr3
M3
25,28380549 26,09605306 1,032125211
HEMOP‐000043 male
36,6136986 Highrisk
bcr1
M3
18,85342741 26,61442667 1,41164925
HEMOP‐000045 male
19,6027397 Highrisk
bcr3
M3v 7,118085855 24,65792136 3,464122499
HEMOP‐000046 male
37,0109589 Lowrisk
bcr3
M3
27,34263918 0,465540648 0,017026178
HEMOP‐000047 female
42,7232877 Intermediaterisk
bcr3
M3
4,36291
0,010978912 0,00251642
HEMOP‐000048 male
39,0684932 Intermediaterisk
bcr1
M3
6,578475
2,572804793 0,391094409
HEMOP‐000049 female
48,2876712 Lowrisk
bcr1
M3
55,80247898 23,73129005 0,425273043
HEMOP‐000050 male
18,6027397 Intermediaterisk
bcr1
M3
96,62124718 117,6894439 1,218049314
HEMOP‐000051 female
34,4219178 Intermediaterisk
bcr1
M3
19,73867186 15,10563855 0,765281406
HEMOP‐000052 female
60,339726
Highrisk
bcr3
M3
12,815626
0,033974205 0,002650998
HEMOP‐000053 male
22,0027397 Lowrisk
bcr1
M3
62,953511
10,98000427 0,174414486
HEMOP‐000054 male
40,9945205 Highrisk
bcr1
M3v 36,249456
0,376082854 0,010374855
HEMOP‐000055 female
21,6
Highrisk
bcr3
M3
HEMOP‐000057 female
25,7643836 Highrisk
bcr3
HEMOP‐000060 female
22,7863014 Highrisk
HEMOP‐000061 female
34,5150685 Intermediaterisk
HEMOP‐000063 female
32,2054795 Intermediaterisk
bcr3
HEMOP‐000065 female
42,4356164 Intermediaterisk
bcr3
HEMOP‐000066 male
47,7780822 Intermediaterisk
M3
33,569873
0,531880068 0,01584397
M3
5,448966
0,540997468 0,099284427
M3
53,451714
0,700824417 0,013111355
M3
22,184739
0,060899977 0,002745129
M3
M3
HEMOP‐000068 female
20,5479452 Highrisk
bcr3
M3
3,727204
0,013643541 0,00366053
SCSP‐000005
female
25,4986301 Lowrisk
bcr3
M3
3,293713
25,56848634 7,762815504
SCSP‐000006
male
48,3671233 Intermediaterisk
bcr3
M3
10,86234536 0,509927341 0,046944497
SCSP‐000008
male
34,5041096 Intermediaterisk
bcr1
M3
1,674973532 0,131019923 0,078222086
SCSP‐000009
female
28,5424658 Lowrisk
bcr1
M3
21,6731392
SCSP‐000010
male
39,3863014 Highrisk
bcr3
M3
58,80540324 2698,344793 45,88600102
0,024421863 0,001126826
SCSP‐000011
female
20,2794521 Highrisk
bcr3
M3v
SCSP‐000014
male
42,4356164 Intermediaterisk
bcr1
M3
24,22603576 19,7036006
SCSP‐000015
male
29,0136986 Highrisk
bcr3
M3
72,941503
Lowrisk
0,813323352
0,111242812 0,001525096
SCSP‐000016
female
47,369863
bcr3
M3
9,993487248 0,005619837 0,00056235
SCSP‐000017
female
65,2328767 Intermediaterisk
bcr1
M3
2,436346
SCSP‐000018
female
23,5726027 Intermediaterisk
bcr1
M3
79,76183658 61,3897082
SCSP‐000020
female
16,369863
bcr1
M3
14,74566119 6,030193447 0,408946969
SCSP‐000021
female
18,8054795 Highrisk
M3v 0,026637
SCSP‐000023
female
65,1589041 Highrisk
NA
Lowrisk
3,232328912 1,326711769
3,75337E‐05
0,769662671
0,001409081
UCAMP‐000001
female
35,5863014 Intermediaterisk
bcr3
M3
115,46528
UCAMP‐000002
female
24,5643836 Intermediaterisk
bcr1
M3
26,85917563 24,60621063 0,916119354
150,8014087 1,306032503
UCAMP‐000003
female
38,4191781 Intermediaterisk
bcr1
M3
20,451532
UCAMP‐000004
male
48,1972603 Highrisk
bcr1
M3
43,89949593 2108,194542 48,02320612
UCAMP‐000005
female
18,3287671 Lowrisk
bcr1
M3
37,48735318 0,231343313 0,006171236
UCAMP‐000006
male
26,4191781 Highrisk
bcr3
M3
2,22905788
UCAMP‐000009
female
27,9835616 Intermediaterisk
bcr3
M3
43,47509374 39,91492073 0,918110056
UCAMP‐000011
male
59,7041096 Intermediaterisk
bcr1
M3
13,09077246 13,8074726
UCAMP‐000012
male
43,5753425 Intermediaterisk
bcr1
M3
18,853427
5,134140051 0,272318664
UCAMP‐000014
female
20,3315068 Intermediaterisk
bcr2
M3
7,118086
4,305476224 0,604864317
UCAMP‐000015
male
40,4246575 Highrisk
bcr1
M3
27,342639
14,49150011 0,529996395
UCAMP‐000016
male
22,4410959 Intermediaterisk
bcr1
M3
5,448965948 68,80638217 12,6274201
17,36465059 0,849063561
16,25703904 7,293233248
1,054748499
UCAMP‐000017
male
60,7041096 Highrisk
bcr1
M3
55,802479
211,7004981 3,793747194
UCAMP‐000018
male
27,3315068 Intermediaterisk
bcr1
M3
96,621247
66,04375769 0,68353245
UCAMP‐000019
male
54,1589041 Intermediaterisk
bcr1
M3
19,738672
7,425129867 0,376171703
UCAMP‐000020
female
27,030137
Highrisk
bcr3
M3
46,434475
3370,738304 72,59128706
UCAMP‐000021
male
36,4328767 Highrisk
bcr3
M3
17,55336974 0,061556744
UCAMP‐000022
female
19,7178082 Intermediaterisk
bcr1
M3
285,157543
UCAMP‐000023
female
52,430137
bcr3
M3
69,60307
0,010779441 0,00015487
UCAMP‐000024
male
26,1424658 Lowrisk
NA
M3
21,079881
0,160257668 0,007602399
Highrisk
UCAMP‐000025
male
34
bcr3
M3
11,13059
0,060297811 0,005417306
UCAMP‐000026
male
24,0054795 Intermediaterisk
Lowrisk
NA
M3
7,411865
0,044176322 0,005960217
UCAMP‐000027
female
35,1726027 Intermediaterisk
bcr3
M3
UCAMP‐000028
female
26,7013699 Lowrisk
bcr1
M3
58,84559
0,0864223
0,001468628
UFMG‐000014
female
34,6657534 Intermediaterisk
bcr1
M3
10,862345
0,530133759 0,048804725
UFMG‐000016
female
36,0356164 Intermediaterisk
bcr2
M3
1,674974
0,475016971 0,283596623
UFMG‐000017
female
55,4164384 Intermediaterisk
bcr2
M3
21,673139
16,37045239 0,755333706
UFMG‐000019
male
18,4547945 Intermediaterisk
bcr1
M3
58,805403
52,50219779 0,892812482
UFMG‐000020
male
19,5232877 Highrisk
bcr3
M3
24,226036
178,8042079 7,380663014
UFMG‐000021
female
41,1589041 Highrisk
bcr3
M3
9,993487
54,30301513 5,433840574
UFMG‐000022
female
54,1506849 Intermediaterisk
bcr1
M3
9,881153122 0,159390964 0,016130806
UFMG‐000023
male
27,8027397 Lowrisk
bcr1
M3
79,761837
UFMG‐000024
female
50,9205479 Lowrisk
bcr1
M3
14,745661
11,28562456 0,765352232
UFMG‐000025
female
33,1424658 Intermediaterisk
M3
5,795769
2,847039574 0,491227234
UFMG‐000026
male
35,2465753 Highrisk
bcr1
M3
12,716674
5,790995281 0,455385998
UFMG‐000027
female
29,5863014 Lowrisk
bcr3
M3
0,042961204 0,000538619
UFMG‐000028
female
26,4630137 Highrisk
bcr3
M3
41,651131
0,000866432 2,08021E‐05
UFMG‐000029
female
24,9643836 Intermediaterisk
bcr3
M3
26,859176
0,160736045 0,0059844
UFMG‐000030
female
30,2684932 Highrisk
bcr1
M3
23,77704
0,301456889 0,012678487
UFMG‐000031
female
36,5726027 Intermediaterisk
bcr1
M3
64,156503
0,031511303 0,000491163
UFMG‐000032
male
37,8849315 Lowrisk
bcr1
M3
12,966109
0,645131267 0,049755194
Unife‐000003
female
22,5917808 Intermediaterisk
bcr1
M3
73,738528
182,3329113 2,472695296
Unife‐000005
male
26,4191781 Intermediaterisk
bcr1
M3
43,899496
1521,369251 34,65573389
Unife‐000009
male
57,6465753 Lowrisk
bcr3
M3
UNIFE‐000010
female
31,9452055 Lowrisk
bcr1
M3
5,786418
0,070746357 0,012226278
UNIFE‐000011
female
50,3506849 Intermediaterisk
NA
M3
193,789839
0,875207979 0,004516274
Supplemental Figure 1 shows the endogenous levels of ΔNp73 and TAp73
proteins in primary APL blasts. Samples #1, #2, #4, and #6 had a low
ΔNp73/TAp73ratioingeneexpressionanalysis,whereassamples#3and#5hada
highΔNp73/TAp73ratio.
Supplemental Figure 1. Western blot analysis of protein extracts from
primary APL blast. Using specific antibodies, immunoblotting analysis
demonstrated that APL samples present several isoform of TAp73 protein (α‐ε)
and truncated ΔNp73 isoform, in different levels. COX IV (cytochrome C oxidase)
primaryantibodywasusedasinternalcontrol.
Survival outcomes: The results from survival outcomes were consistent
withtheresultfromamultivariableproportionalhazardsmodeladjustingforage,
WBC counts, gender, and albumin levels as possible confounders (Supplemental
Table 2). The Cox proportional hazard model demonstrated that the
ΔNp73/TAp73ratiowasindependentlyassociatedwithshortersurvival.
SupplementalTable2.MultivariableCoxmodelforoverallsurvival
Variable
HR 95%CI
Pvalue
Age(y):continuousvariable
1.04 1.01 1.08 .0097
Gender:femaleversusmale
3.04 1.08 8.54 .035
WBCcounts(×109/L):continuousvariable 1.02 1.01 1.03 .0086
3.45 1.37 8.70 .0087
Albuminlevels(g/dL):3.5versus>3.5
ΔNp73/TAp73ratio:Q4versus Q1–Q3
4.47 1.64 12.2 .0035
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