Uterine Corpus Endometrioid Carcinoma: Correlation between gene mutation status and selected clinical features<BR>(primary solid tumor cohort)

Uterine Corpus Endometrioid Carcinoma: Correlation between gene mutation status and selected clinical features
(primary solid tumor cohort)

Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)

Overview

Introduction

This pipeline computes the correlation between significantly recurrent gene mutations and selected clinical features.

Summary

Testing the association between mutation status of 69 genes and 4 clinical features across 248 patients, 10 significant findings detected with Q value < 0.25.

PTEN mutation correlated to 'HISTOLOGICAL.TYPE'.
TP53 mutation correlated to 'AGE' and 'HISTOLOGICAL.TYPE'.
KRAS mutation correlated to 'AGE'.
PIK3R1 mutation correlated to 'HISTOLOGICAL.TYPE'.
CTNNB1 mutation correlated to 'HISTOLOGICAL.TYPE'.
CYLC1 mutation correlated to 'HISTOLOGICAL.TYPE'.
STEAP4 mutation correlated to 'HISTOLOGICAL.TYPE'.
ANKRD31 mutation correlated to 'HISTOLOGICAL.TYPE'.
ZNF69 mutation correlated to 'HISTOLOGICAL.TYPE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 69 genes and 4 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 10 significant findings detected.


		Clinical Features	Time to Death	AGE	HISTOLOGICAL TYPE	RADIATIONS RADIATION REGIMENINDICATION
	nMutated (%)	nWild-Type	logrank test	t-test	Chi-square test	Fisher's exact test
TP53	69 (28%)	179	0.325 (1.00)	6.15e-06 (0.00168)	3.98e-23 (1.1e-20)	0.371 (1.00)
PTEN	161 (65%)	87	0.19 (1.00)	0.0276 (1.00)	5.44e-19 (1.5e-16)	0.0503 (1.00)
KRAS	53 (21%)	195	0.072 (1.00)	0.000274 (0.0739)	0.00692 (1.00)	0.253 (1.00)
PIK3R1	83 (33%)	165	0.871 (1.00)	0.806 (1.00)	0.000827 (0.221)	0.395 (1.00)
CTNNB1	74 (30%)	174	0.878 (1.00)	0.0017 (0.449)	1.04e-05 (0.00284)	0.381 (1.00)
CYLC1	18 (7%)	230	0.198 (1.00)	0.765 (1.00)	0.000601 (0.162)	0.313 (1.00)
STEAP4	12 (5%)	236	0.286 (1.00)	0.933 (1.00)	0.000714 (0.191)	0.756 (1.00)
ANKRD31	16 (6%)	232	0.234 (1.00)	0.883 (1.00)	9.81e-05 (0.0267)	0.588 (1.00)
ZNF69	7 (3%)	241	0.514 (1.00)	0.0163 (1.00)	0.000147 (0.0397)	1 (1.00)
ARID1A	83 (33%)	165	0.008 (1.00)	0.00721 (1.00)	0.00127 (0.337)	0.673 (1.00)
FGFR2	31 (12%)	217	0.9 (1.00)	0.998 (1.00)	0.719 (1.00)	1 (1.00)
PIK3CA	132 (53%)	116	0.055 (1.00)	0.195 (1.00)	0.555 (1.00)	0.593 (1.00)
CTCF	45 (18%)	203	0.405 (1.00)	0.0198 (1.00)	0.0021 (0.552)	0.863 (1.00)
FBXW7	39 (16%)	209	0.772 (1.00)	0.904 (1.00)	0.0473 (1.00)	0.855 (1.00)
SPOP	21 (8%)	227	0.65 (1.00)	0.527 (1.00)	0.332 (1.00)	0.811 (1.00)
PPP2R1A	27 (11%)	221	0.121 (1.00)	0.0374 (1.00)	0.00977 (1.00)	0.52 (1.00)
CHD4	35 (14%)	213	0.361 (1.00)	0.418 (1.00)	0.779 (1.00)	0.565 (1.00)
P2RY11	9 (4%)	239	0.395 (1.00)	0.396 (1.00)	0.987 (1.00)	0.497 (1.00)
CCND1	15 (6%)	233	0.729 (1.00)	0.0556 (1.00)	0.413 (1.00)	0.4 (1.00)
NFE2L2	15 (6%)	233	0.903 (1.00)	0.191 (1.00)	0.447 (1.00)	0.589 (1.00)
FOXA2	12 (5%)	236	0.799 (1.00)	0.531 (1.00)	0.972 (1.00)	0.229 (1.00)
FAM9A	14 (6%)	234	0.378 (1.00)	0.913 (1.00)	0.89 (1.00)	1 (1.00)
SOX17	7 (3%)	241	0.669 (1.00)	0.848 (1.00)	0.00567 (1.00)	0.428 (1.00)
MAX	11 (4%)	237	0.889 (1.00)	0.336 (1.00)	0.404 (1.00)	0.753 (1.00)
ZNF267	16 (6%)	232	0.565 (1.00)	0.207 (1.00)	0.0275 (1.00)	0.79 (1.00)
RBMX	13 (5%)	235	0.336 (1.00)	0.161 (1.00)	0.4 (1.00)	0.142 (1.00)
MORC4	20 (8%)	228	0.152 (1.00)	0.0204 (1.00)	0.629 (1.00)	1 (1.00)
OR4K2	11 (4%)	237	0.304 (1.00)	0.241 (1.00)	0.00658 (1.00)	1 (1.00)
ARID5B	29 (12%)	219	0.642 (1.00)	0.649 (1.00)	0.00865 (1.00)	1 (1.00)
OR5D13	10 (4%)	238	0.895 (1.00)	0.741 (1.00)	0.188 (1.00)	0.318 (1.00)
OR5AS1	10 (4%)	238	0.675 (1.00)	0.503 (1.00)	0.396 (1.00)	0.501 (1.00)
OR4A15	13 (5%)	235	0.213 (1.00)	0.167 (1.00)	0.00219 (0.573)	1 (1.00)
CSDE1	21 (8%)	227	0.802 (1.00)	0.294 (1.00)	0.0435 (1.00)	1 (1.00)
CTXN3	6 (2%)	242	0.512 (1.00)	0.794 (1.00)	0.548 (1.00)	1 (1.00)
PAPD4	13 (5%)	235	0.982 (1.00)	0.181 (1.00)	0.962 (1.00)	0.378 (1.00)
RPL14	7 (3%)	241	0.532 (1.00)	0.677 (1.00)	0.991 (1.00)	0.428 (1.00)
DNER	18 (7%)	230	0.746 (1.00)	0.0414 (1.00)	0.0324 (1.00)	0.44 (1.00)
RASA1	22 (9%)	226	0.127 (1.00)	0.466 (1.00)	0.0211 (1.00)	0.639 (1.00)
TAB3	18 (7%)	230	0.22 (1.00)	0.107 (1.00)	0.00686 (1.00)	0.616 (1.00)
UPF3B	16 (6%)	232	0.735 (1.00)	0.81 (1.00)	0.395 (1.00)	0.588 (1.00)
SGK1	15 (6%)	233	0.925 (1.00)	0.427 (1.00)	0.759 (1.00)	0.158 (1.00)
C1ORF100	9 (4%)	239	0.344 (1.00)	0.246 (1.00)	0.376 (1.00)	0.497 (1.00)
ZNF334	17 (7%)	231	0.95 (1.00)	0.0232 (1.00)	0.787 (1.00)	1 (1.00)
METTL14	10 (4%)	238	0.358 (1.00)	0.833 (1.00)	0.707 (1.00)	1 (1.00)
NRAS	9 (4%)	239	0.354 (1.00)	0.616 (1.00)	0.0289 (1.00)	0.722 (1.00)
HIST1H2BD	6 (2%)	242	0.0836 (1.00)	0.474 (1.00)	0.897 (1.00)	0.415 (1.00)
CLIC2	10 (4%)	238	0.294 (1.00)	0.855 (1.00)	0.00231 (0.601)	1 (1.00)
CNPY1	7 (3%)	241	0.449 (1.00)	0.18 (1.00)	0.294 (1.00)	1 (1.00)
RAE1	11 (4%)	237	0.282 (1.00)	0.603 (1.00)	0.0127 (1.00)	0.34 (1.00)
IGFBP7	6 (2%)	242	0.406 (1.00)	0.659 (1.00)	0.228 (1.00)	0.667 (1.00)
ZNF300	15 (6%)	233	0.222 (1.00)	0.338 (1.00)	0.135 (1.00)	0.275 (1.00)
SNTG1	11 (4%)	237	0.307 (1.00)	0.506 (1.00)	0.0644 (1.00)	0.753 (1.00)
SSX5	11 (4%)	237	0.328 (1.00)	0.15 (1.00)	0.00658 (1.00)	1 (1.00)
FMR1	16 (6%)	232	0.304 (1.00)	0.643 (1.00)	0.0688 (1.00)	0.588 (1.00)
GYPB	5 (2%)	243	0.583 (1.00)	0.843 (1.00)	0.149 (1.00)	0.168 (1.00)
LRRIQ3	12 (5%)	236	0.372 (1.00)	0.00386 (1)	0.00221 (0.578)	0.229 (1.00)
NDN	6 (2%)	242	0.535 (1.00)	0.487 (1.00)	0.699 (1.00)	1 (1.00)
C14ORF118	15 (6%)	233	0.268 (1.00)	0.0138 (1.00)	0.369 (1.00)	0.589 (1.00)
COX19	4 (2%)	244	0.652 (1.00)	0.269 (1.00)	0.998 (1.00)	1 (1.00)
GNPDA2	8 (3%)	240	0.789 (1.00)	0.175 (1.00)	0.518 (1.00)	0.451 (1.00)
GPM6A	11 (4%)	237	0.306 (1.00)	0.502 (1.00)	0.545 (1.00)	1 (1.00)
ZNF449	12 (5%)	236	0.355 (1.00)	0.95 (1.00)	0.655 (1.00)	0.552 (1.00)
OR2M3	10 (4%)	238	0.315 (1.00)	0.822 (1.00)	0.707 (1.00)	0.739 (1.00)
XPA	7 (3%)	241	0.169 (1.00)	0.9 (1.00)	0.981 (1.00)	0.236 (1.00)
BRS3	15 (6%)	233	0.184 (1.00)	0.133 (1.00)	0.025 (1.00)	0.4 (1.00)
GK2	17 (7%)	231	0.202 (1.00)	0.334 (1.00)	0.0119 (1.00)	0.432 (1.00)
TPTE	15 (6%)	233	0.273 (1.00)	0.167 (1.00)	0.00648 (1.00)	1 (1.00)
IL24	7 (3%)	241	0.426 (1.00)	0.988 (1.00)	0.00148 (0.392)	0.428 (1.00)
CCDC160	11 (4%)	237	0.271 (1.00)	0.34 (1.00)	0.00658 (1.00)	1 (1.00)

'PTEN MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 5.44e-19 (Chi-square test), Q value = 1.5e-16

Table S1. Gene #4: 'PTEN MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3)	MIXED SEROUS AND ENDOMETRIOID	SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL	182	3	8	2	5	4	44
PTEN MUTATED	146	2	6	1	4	1	1
PTEN WILD-TYPE	36	1	2	1	1	3	43

Figure S1. Get High-res Image Gene #4: 'PTEN MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'TP53 MUTATION STATUS' versus 'AGE'

P value = 6.15e-06 (t-test), Q value = 0.0017

Table S2. Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	248	63.1 (11.1)
TP53 MUTATED	69	67.9 (9.4)
TP53 WILD-TYPE	179	61.3 (11.2)

Figure S2. Get High-res Image Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'TP53 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 3.98e-23 (Chi-square test), Q value = 1.1e-20

Table S3. Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3)	MIXED SEROUS AND ENDOMETRIOID	SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL	182	3	8	2	5	4	44
TP53 MUTATED	23	0	0	0	4	3	39
TP53 WILD-TYPE	159	3	8	2	1	1	5

Figure S3. Get High-res Image Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'KRAS MUTATION STATUS' versus 'AGE'

P value = 0.000274 (t-test), Q value = 0.074

Table S4. Gene #7: 'KRAS MUTATION STATUS' versus Clinical Feature #2: 'AGE'

	nPatients	Mean (Std.Dev)
ALL	248	63.1 (11.1)
KRAS MUTATED	53	58.8 (8.7)
KRAS WILD-TYPE	195	64.3 (11.4)

Figure S4. Get High-res Image Gene #7: 'KRAS MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'PIK3R1 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 0.000827 (Chi-square test), Q value = 0.22

Table S5. Gene #8: 'PIK3R1 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3)	MIXED SEROUS AND ENDOMETRIOID	SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL	182	3	8	2	5	4	44
PIK3R1 MUTATED	73	2	3	0	2	1	2
PIK3R1 WILD-TYPE	109	1	5	2	3	3	42

Figure S5. Get High-res Image Gene #8: 'PIK3R1 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'CTNNB1 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 1.04e-05 (Chi-square test), Q value = 0.0028

Table S6. Gene #9: 'CTNNB1 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3)	MIXED SEROUS AND ENDOMETRIOID	SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL	182	3	8	2	5	4	44
CTNNB1 MUTATED	69	1	2	2	0	0	0
CTNNB1 WILD-TYPE	113	2	6	0	5	4	44

Figure S6. Get High-res Image Gene #9: 'CTNNB1 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'CYLC1 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 0.000601 (Chi-square test), Q value = 0.16

Table S7. Gene #22: 'CYLC1 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3)	MIXED SEROUS AND ENDOMETRIOID	SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL	182	3	8	2	5	4	44
CYLC1 MUTATED	14	0	0	0	3	0	1
CYLC1 WILD-TYPE	168	3	8	2	2	4	43

Figure S7. Get High-res Image Gene #22: 'CYLC1 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'STEAP4 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 0.000714 (Chi-square test), Q value = 0.19

Table S8. Gene #44: 'STEAP4 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3)	MIXED SEROUS AND ENDOMETRIOID	SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL	182	3	8	2	5	4	44
STEAP4 MUTATED	8	0	2	0	2	0	0
STEAP4 WILD-TYPE	174	3	6	2	3	4	44

Figure S8. Get High-res Image Gene #44: 'STEAP4 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'ANKRD31 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 9.81e-05 (Chi-square test), Q value = 0.027

Table S9. Gene #46: 'ANKRD31 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3)	MIXED SEROUS AND ENDOMETRIOID	SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL	182	3	8	2	5	4	44
ANKRD31 MUTATED	12	0	1	0	3	0	0
ANKRD31 WILD-TYPE	170	3	7	2	2	4	44

Figure S9. Get High-res Image Gene #46: 'ANKRD31 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'ZNF69 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 0.000147 (Chi-square test), Q value = 0.04

Table S10. Gene #64: 'ZNF69 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

nPatients	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1 OR 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 1)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 2)	ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA (GRADE 3)	MIXED SEROUS AND ENDOMETRIOID	SEROUS ENDOMETRIAL ADENOCARCINOMA
ALL	182	3	8	2	5	4	44
ZNF69 MUTATED	5	0	0	0	2	0	0
ZNF69 WILD-TYPE	177	3	8	2	3	4	44

Figure S10. Get High-res Image Gene #64: 'ZNF69 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

Methods & Data

Input

Mutation data file = UCEC-TP.mutsig.cluster.txt
Clinical data file = UCEC-TP.clin.merged.picked.txt
Number of patients = 248
Number of significantly mutated genes = 69
Number of selected clinical features = 4
Exclude genes that fewer than K tumors have mutations, K = 3

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene mutations were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R

Student's t-test analysis

For continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between tumors with and without gene mutations using 't.test' function in R

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.test' function in R

Fisher's exact test

For binary or multi-class clinical features (nominal or ordinal), two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.test' function in R

Q value calculation

For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

References

[1] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)

[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)

[3] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)

[4] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)

[5] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)

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