Uterine Corpus Endometrioid Carcinoma: Correlation between gene mutation status and selected clinical features

Maintained by TCGA GDAC Team (Broad Institute/Dana-Farber Cancer Institute/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 63 genes and 5 clinical features across 248 patients, 6 significant findings detected with Q value < 0.25.

OR10X1 mutation correlated to 'HISTOLOGICAL.TYPE'.
ZNF69 mutation correlated to 'HISTOLOGICAL.TYPE'.
TREM2 mutation correlated to 'HISTOLOGICAL.TYPE'.
ZMYND10 mutation correlated to 'HISTOLOGICAL.TYPE'.
CEACAM4 mutation correlated to 'HISTOLOGICAL.TYPE'.
PPP2CA mutation correlated to 'HISTOLOGICAL.TYPE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 63 genes and 5 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 6 significant findings detected.


		Clinical Features	Time to Death	AGE	HISTOLOGICAL TYPE	RADIATIONS RADIATION REGIMENINDICATION	NEOADJUVANT THERAPY
	nMutated (%)	nWild-Type	logrank test	t-test	Chi-square test	Fisher's exact test	Fisher's exact test
OR10X1	7 (3%)	241	0.646 (1.00)	0.036 (1.00)	0.000147 (0.0458)	0.428 (1.00)	1 (1.00)
ZNF69	7 (3%)	241	0.514 (1.00)	0.0163 (1.00)	0.000147 (0.0458)	1 (1.00)	0.396 (1.00)
TREM2	7 (3%)	241	0.361 (1.00)	0.197 (1.00)	0.000147 (0.0458)	0.236 (1.00)	1 (1.00)
ZMYND10	7 (3%)	241	0.384 (1.00)	0.956 (1.00)	2.1e-11 (6.62e-09)	1 (1.00)	1 (1.00)
CEACAM4	6 (2%)	242	0.554 (1.00)	0.0488 (1.00)	2.07e-05 (0.0065)	0.667 (1.00)	0.667 (1.00)
PPP2CA	6 (2%)	242	0.494 (1.00)	0.0624 (1.00)	2.77e-05 (0.00868)	0.667 (1.00)	0.35 (1.00)
TNFAIP6	12 (5%)	236	0.819 (1.00)	0.302 (1.00)	0.6 (1.00)	1 (1.00)	0.741 (1.00)
RPL14	7 (3%)	241	0.532 (1.00)	0.677 (1.00)	0.991 (1.00)	0.428 (1.00)	0.396 (1.00)
IK	8 (3%)	240	0.734 (1.00)	0.629 (1.00)	0.809 (1.00)	1 (1.00)	0.22 (1.00)
CCDC160	11 (4%)	237	0.271 (1.00)	0.34 (1.00)	0.00658 (1.00)	1 (1.00)	0.732 (1.00)
PRPF38B	11 (4%)	237	0.39 (1.00)	0.482 (1.00)	0.623 (1.00)	0.753 (1.00)	1 (1.00)
NKTR	18 (7%)	230	0.194 (1.00)	0.263 (1.00)	0.0375 (1.00)	0.616 (1.00)	0.786 (1.00)
SARNP	5 (2%)	243	0.496 (1.00)	0.656 (1.00)	0.461 (1.00)	0.663 (1.00)	1 (1.00)
C1ORF189	4 (2%)	244	0.652 (1.00)	0.2 (1.00)	0.078 (1.00)	1 (1.00)	0.0639 (1.00)
ZNF564	9 (4%)	239	0.32 (1.00)	0.44 (1.00)	0.00167 (0.515)	0.497 (1.00)	0.451 (1.00)
USP48	13 (5%)	235	0.257 (1.00)	0.0295 (1.00)	0.4 (1.00)	1 (1.00)	0.524 (1.00)
LGI2	9 (4%)	239	0.467 (1.00)	0.882 (1.00)	0.0573 (1.00)	0.281 (1.00)	1 (1.00)
LINGO4	10 (4%)	238	0.407 (1.00)	0.0353 (1.00)	0.707 (1.00)	0.739 (1.00)	0.468 (1.00)
SERPINB9	8 (3%)	240	0.464 (1.00)	0.0216 (1.00)	0.628 (1.00)	0.451 (1.00)	0.111 (1.00)
FRMD6	11 (4%)	237	0.357 (1.00)	0.501 (1.00)	0.653 (1.00)	0.518 (1.00)	0.499 (1.00)
TRIM46	9 (4%)	239	0.546 (1.00)	0.413 (1.00)	0.987 (1.00)	1 (1.00)	1 (1.00)
SEPT5	8 (3%)	240	0.585 (1.00)	0.743 (1.00)	0.833 (1.00)	0.719 (1.00)	1 (1.00)
ABCB6	10 (4%)	238	0.316 (1.00)	0.913 (1.00)	0.315 (1.00)	1 (1.00)	0.293 (1.00)
KRT32	10 (4%)	238	0.834 (1.00)	0.822 (1.00)	0.00363 (1.00)	0.739 (1.00)	0.468 (1.00)
VSIG1	7 (3%)	241	0.442 (1.00)	0.279 (1.00)	0.856 (1.00)	0.694 (1.00)	1 (1.00)
ZBTB33	15 (6%)	233	0.327 (1.00)	0.231 (1.00)	0.827 (1.00)	0.589 (1.00)	0.766 (1.00)
CIC	17 (7%)	231	0.285 (1.00)	0.647 (1.00)	0.0741 (1.00)	0.599 (1.00)	0.166 (1.00)
ERBB3	17 (7%)	231	0.311 (1.00)	0.653 (1.00)	0.0843 (1.00)	0.599 (1.00)	1 (1.00)
HFE	6 (2%)	242	0.547 (1.00)	0.832 (1.00)	0.996 (1.00)	0.415 (1.00)	1 (1.00)
MTSS1	11 (4%)	237	0.457 (1.00)	0.272 (1.00)	0.404 (1.00)	0.194 (1.00)	0.732 (1.00)
OR4L1	10 (4%)	238	0.93 (1.00)	0.11 (1.00)	0.456 (1.00)	0.0959 (1.00)	0.732 (1.00)
RDH8	8 (3%)	240	0.507 (1.00)	0.272 (1.00)	0.518 (1.00)	0.451 (1.00)	0.452 (1.00)
BTG4	7 (3%)	241	0.46 (1.00)	0.855 (1.00)	0.294 (1.00)	0.694 (1.00)	0.677 (1.00)
MLN	6 (2%)	242	0.498 (1.00)	0.539 (1.00)	0.897 (1.00)	1 (1.00)	1 (1.00)
RAP2C	5 (2%)	243	0.616 (1.00)	0.797 (1.00)	0.933 (1.00)	0.0483 (1.00)	0.327 (1.00)
PITRM1	13 (5%)	235	0.702 (1.00)	0.775 (1.00)	0.015 (1.00)	0.039 (1.00)	0.756 (1.00)
OR6B1	6 (2%)	242	0.524 (1.00)	0.654 (1.00)	0.897 (1.00)	0.415 (1.00)	1 (1.00)
BCL7C	5 (2%)	243	0.369 (1.00)	0.251 (1.00)	0.149 (1.00)	0.663 (1.00)	1 (1.00)
CPA5	7 (3%)	241	0.399 (1.00)	0.0488 (1.00)	0.294 (1.00)	1 (1.00)	0.396 (1.00)
CFHR5	8 (3%)	240	0.39 (1.00)	0.958 (1.00)	0.343 (1.00)	0.719 (1.00)	1 (1.00)
RGL2	7 (3%)	241	0.636 (1.00)	0.762 (1.00)	0.856 (1.00)	0.428 (1.00)	0.677 (1.00)
PSG9	5 (2%)	243	0.515 (1.00)	0.508 (1.00)	0.193 (1.00)	1 (1.00)	0.617 (1.00)
CD4	6 (2%)	242	0.496 (1.00)	0.517 (1.00)	0.897 (1.00)	0.667 (1.00)	0.667 (1.00)
IL27	4 (2%)	244	0.612 (1.00)	0.919 (1.00)	0.961 (1.00)	0.302 (1.00)	0.577 (1.00)
HOXA1	7 (3%)	241	0.505 (1.00)	0.457 (1.00)	0.785 (1.00)	0.236 (1.00)	0.195 (1.00)
SLCO2A1	9 (4%)	239	0.81 (1.00)	0.983 (1.00)	0.376 (1.00)	0.722 (1.00)	0.451 (1.00)
C20ORF112	6 (2%)	242	0.165 (1.00)	0.785 (1.00)	0.897 (1.00)	1 (1.00)	1 (1.00)
PRKRA	4 (2%)	244	0.512 (1.00)	0.498 (1.00)	0.998 (1.00)	0.608 (1.00)	0.577 (1.00)
LIMA1	8 (3%)	240	0.452 (1.00)	0.821 (1.00)	0.343 (1.00)	0.719 (1.00)	0.452 (1.00)
MS4A6A	4 (2%)	244	0.497 (1.00)	0.39 (1.00)	0.0702 (1.00)	1 (1.00)	1 (1.00)
PREB	5 (2%)	243	0.496 (1.00)	0.252 (1.00)	0.933 (1.00)	0.342 (1.00)	1 (1.00)
ATP6AP1	8 (3%)	240	0.444 (1.00)	0.74 (1.00)	0.343 (1.00)	0.451 (1.00)	1 (1.00)
C20ORF4	5 (2%)	243	0.482 (1.00)	0.864 (1.00)	0.933 (1.00)	0.342 (1.00)	0.617 (1.00)
GTSF1	3 (1%)	245	0.648 (1.00)	0.547 (1.00)	0.981 (1.00)	1 (1.00)	0.564 (1.00)
SEMG2	11 (4%)	237	0.337 (1.00)	0.111 (1.00)	0.354 (1.00)	1 (1.00)	1 (1.00)
CHST10	5 (2%)	243	0.47 (1.00)	0.985 (1.00)	0.933 (1.00)	0.342 (1.00)	0.327 (1.00)
HINT3	4 (2%)	244	0.67 (1.00)	0.518 (1.00)	0.328 (1.00)	1 (1.00)	0.577 (1.00)
OIP5	3 (1%)	245	0.848 (1.00)	0.642 (1.00)	0.981 (1.00)	0.271 (1.00)	0.564 (1.00)
TMEM212	3 (1%)	245	0.655 (1.00)	0.396 (1.00)	0.0134 (1.00)	0.553 (1.00)	0.564 (1.00)
NDUFB7	3 (1%)	245	0.648 (1.00)	0.811 (1.00)	0.159 (1.00)	0.0393 (1.00)	1 (1.00)
NDUFAF1	9 (4%)	239	0.351 (1.00)	0.83 (1.00)	0.376 (1.00)	0.497 (1.00)	1 (1.00)
CASP10	7 (3%)	241	0.478 (1.00)	0.416 (1.00)	0.294 (1.00)	1 (1.00)	0.677 (1.00)
PLAC8L1	5 (2%)	243	0.45 (1.00)	0.545 (1.00)	0.149 (1.00)	0.342 (1.00)	0.617 (1.00)

'OR10X1 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 0.000147 (Chi-square test), Q value = 0.046

Table S1. Gene #9: 'OR10X1 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
OR10X1 MUTATED	5	0	0	0	2	0	0
OR10X1 WILD-TYPE	177	3	8	2	3	4	44

Figure S1. Get High-res Image Gene #9: 'OR10X1 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'ZNF69 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 0.000147 (Chi-square test), Q value = 0.046

Table S2. Gene #22: '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 S2. Get High-res Image Gene #22: 'ZNF69 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'TREM2 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 0.000147 (Chi-square test), Q value = 0.046

Table S3. Gene #29: 'TREM2 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
TREM2 MUTATED	5	0	0	0	2	0	0
TREM2 WILD-TYPE	177	3	8	2	3	4	44

Figure S3. Get High-res Image Gene #29: 'TREM2 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'ZMYND10 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 2.1e-11 (Chi-square test), Q value = 6.6e-09

Table S4. Gene #37: 'ZMYND10 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
ZMYND10 MUTATED	4	0	0	0	3	0	0
ZMYND10 WILD-TYPE	178	3	8	2	2	4	44

Figure S4. Get High-res Image Gene #37: 'ZMYND10 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'CEACAM4 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 2.07e-05 (Chi-square test), Q value = 0.0065

Table S5. Gene #57: 'CEACAM4 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
CEACAM4 MUTATED	4	0	0	0	2	0	0
CEACAM4 WILD-TYPE	178	3	8	2	3	4	44

Figure S5. Get High-res Image Gene #57: 'CEACAM4 MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

'PPP2CA MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 2.77e-05 (Chi-square test), Q value = 0.0087

Table S6. Gene #63: 'PPP2CA 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
PPP2CA MUTATED	3	0	0	0	2	0	1
PPP2CA WILD-TYPE	179	3	8	2	3	4	43

Figure S6. Get High-res Image Gene #63: 'PPP2CA MUTATION STATUS' versus Clinical Feature #3: 'HISTOLOGICAL.TYPE'

Methods & Data

Input

Mutation data file = UCEC.mutsig.cluster.txt
Clinical data file = UCEC.clin.merged.picked.txt
Number of patients = 248
Number of significantly mutated genes = 63
Number of selected clinical features = 5
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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