Correlation between gene mutation status and selected clinical features

Colorectal Adenocarcinoma (Primary solid tumor)

17 October 2014 | analyses__2014_10_17

Maintainer Information

Citation Information

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

Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1M61J32

Overview

Introduction

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

Summary

Testing the association between mutation status of 46 genes and 11 clinical features across 223 patients, 4 significant findings detected with Q value < 0.25.

TP53 mutation correlated to 'HISTOLOGICAL.TYPE'.
BRAF mutation correlated to 'HISTOLOGICAL.TYPE'.
PCDHA3 mutation correlated to 'NEOPLASM.DISEASESTAGE'.
ESR1 mutation correlated to 'NEOPLASM.DISEASESTAGE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 46 genes and 11 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 4 significant findings detected.


		Clinical Features	Time to Death	AGE	PRIMARY SITE OF DISEASE	NEOPLASM DISEASESTAGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	PATHOLOGY M STAGE	GENDER	HISTOLOGICAL TYPE	COMPLETENESS OF RESECTION	NUMBER OF LYMPH NODES
	nMutated (%)	nWild-Type	logrank test	Wilcoxon-test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Wilcoxon-test
TP53	117 (52%)	106	0.361 (1.00)	0.0701 (1.00)	0.0194 (1.00)	0.605 (1.00)	0.963 (1.00)	0.45 (1.00)	0.92 (1.00)	0.423 (1.00)	0.00024 (0.121)	0.583 (1.00)	0.157 (1.00)
BRAF	21 (9%)	202	0.205 (1.00)	0.00407 (1.00)	0.00524 (1.00)	0.131 (1.00)	0.057 (1.00)	0.903 (1.00)	0.386 (1.00)	0.0369 (1.00)	1e-05 (0.00506)	0.605 (1.00)	0.888 (1.00)
PCDHA3	12 (5%)	211	0.0622 (1.00)	0.426 (1.00)	0.352 (1.00)	1e-05 (0.00506)	0.0409 (1.00)	0.376 (1.00)	0.673 (1.00)	0.558 (1.00)	0.717 (1.00)	0.0929 (1.00)	0.81 (1.00)
ESR1	11 (5%)	212	0.681 (1.00)	0.796 (1.00)	0.0197 (1.00)	6e-05 (0.0302)	0.0236 (1.00)	0.568 (1.00)	0.39 (1.00)	1 (1.00)	0.0513 (1.00)	0.652 (1.00)	0.671 (1.00)
APC	163 (73%)	60	0.256 (1.00)	0.113 (1.00)	0.101 (1.00)	0.849 (1.00)	0.932 (1.00)	0.776 (1.00)	0.757 (1.00)	0.0346 (1.00)	0.342 (1.00)	0.522 (1.00)	0.556 (1.00)
KRAS	97 (43%)	126	0.241 (1.00)	0.139 (1.00)	0.0392 (1.00)	0.71 (1.00)	0.305 (1.00)	0.252 (1.00)	0.169 (1.00)	0.687 (1.00)	0.102 (1.00)	0.0319 (1.00)	0.149 (1.00)
NRAS	20 (9%)	203	0.983 (1.00)	0.0543 (1.00)	0.623 (1.00)	0.271 (1.00)	0.293 (1.00)	0.0374 (1.00)	0.546 (1.00)	0.0357 (1.00)	1 (1.00)	0.471 (1.00)	0.879 (1.00)
SMAD4	26 (12%)	197	0.516 (1.00)	0.837 (1.00)	1 (1.00)	0.911 (1.00)	0.877 (1.00)	1 (1.00)	0.795 (1.00)	0.838 (1.00)	0.012 (1.00)	0.832 (1.00)	0.811 (1.00)
FBXW7	38 (17%)	185	0.475 (1.00)	0.0177 (1.00)	0.34 (1.00)	0.0101 (1.00)	0.119 (1.00)	0.775 (1.00)	0.00429 (1.00)	0.374 (1.00)	0.0281 (1.00)	0.0346 (1.00)	0.888 (1.00)
SMAD2	15 (7%)	208	0.962 (1.00)	0.775 (1.00)	0.78 (1.00)	0.00955 (1.00)	0.368 (1.00)	0.271 (1.00)	1 (1.00)	0.291 (1.00)	0.379 (1.00)	0.749 (1.00)	0.0892 (1.00)
FAM123B	24 (11%)	199	0.0384 (1.00)	0.49 (1.00)	0.351 (1.00)	0.696 (1.00)	0.77 (1.00)	0.336 (1.00)	0.59 (1.00)	1 (1.00)	0.747 (1.00)	0.634 (1.00)	0.905 (1.00)
PIK3CA	33 (15%)	190	0.736 (1.00)	0.147 (1.00)	0.226 (1.00)	0.0422 (1.00)	0.916 (1.00)	0.0217 (1.00)	0.132 (1.00)	0.851 (1.00)	0.0258 (1.00)	0.305 (1.00)	0.00377 (1.00)
TCF7L2	18 (8%)	205	0.319 (1.00)	0.253 (1.00)	0.785 (1.00)	0.676 (1.00)	0.336 (1.00)	0.943 (1.00)	0.736 (1.00)	0.624 (1.00)	0.495 (1.00)	0.578 (1.00)	0.757 (1.00)
ARID1A	20 (9%)	203	0.877 (1.00)	0.267 (1.00)	0.623 (1.00)	0.00844 (1.00)	0.139 (1.00)	0.0176 (1.00)	0.383 (1.00)	0.349 (1.00)	0.478 (1.00)	0.602 (1.00)	0.0405 (1.00)
MGC42105	11 (5%)	212	0.55 (1.00)	0.701 (1.00)	0.179 (1.00)	0.175 (1.00)	0.305 (1.00)	0.461 (1.00)	0.392 (1.00)	0.761 (1.00)	0.414 (1.00)	1 (1.00)	0.146 (1.00)
ACVR1B	14 (6%)	209	0.57 (1.00)	0.799 (1.00)	0.0692 (1.00)	0.127 (1.00)	0.0403 (1.00)	1 (1.00)	0.717 (1.00)	1 (1.00)	0.0214 (1.00)	1 (1.00)	0.903 (1.00)
CDC27	13 (6%)	210	0.223 (1.00)	0.687 (1.00)	0.759 (1.00)	0.476 (1.00)	0.721 (1.00)	0.53 (1.00)	0.718 (1.00)	0.154 (1.00)	0.563 (1.00)	1 (1.00)	0.23 (1.00)
KIAA1804	15 (7%)	208	0.344 (1.00)	0.921 (1.00)	0.0181 (1.00)	0.71 (1.00)	0.732 (1.00)	0.345 (1.00)	1 (1.00)	0.425 (1.00)	0.0226 (1.00)	0.747 (1.00)	0.405 (1.00)
PCDHGB1	8 (4%)	215	0.294 (1.00)	0.357 (1.00)	0.44 (1.00)	0.0197 (1.00)	0.149 (1.00)	0.892 (1.00)	0.614 (1.00)	0.485 (1.00)	0.463 (1.00)	0.639 (1.00)	0.897 (1.00)
PCBP1	5 (2%)	218	0.397 (1.00)	0.0546 (1.00)	1 (1.00)	0.0806 (1.00)	0.526 (1.00)	0.694 (1.00)	0.0246 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.348 (1.00)
ZHX2	10 (4%)	213	0.217 (1.00)	0.223 (1.00)	0.727 (1.00)	0.152 (1.00)	0.128 (1.00)	0.182 (1.00)	1 (1.00)	1 (1.00)	0.794 (1.00)	1 (1.00)	0.314 (1.00)
PCDHA2	12 (5%)	211	0.614 (1.00)	0.905 (1.00)	1 (1.00)	0.153 (1.00)	0.0605 (1.00)	0.374 (1.00)	0.266 (1.00)	0.239 (1.00)	0.22 (1.00)	1 (1.00)	0.851 (1.00)
ELF3	8 (4%)	215	0.812 (1.00)	0.0634 (1.00)	0.704 (1.00)	0.892 (1.00)	0.26 (1.00)	0.786 (1.00)	0.34 (1.00)	0.723 (1.00)	1 (1.00)	0.343 (1.00)	0.472 (1.00)
CRTC1	4 (2%)	219	0.361 (1.00)	0.0255 (1.00)	1 (1.00)	0.735 (1.00)	0.193 (1.00)	0.644 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.438 (1.00)
CASP8	10 (4%)	213	0.806 (1.00)	0.0404 (1.00)	0.0336 (1.00)	0.177 (1.00)	0.104 (1.00)	0.141 (1.00)	0.393 (1.00)	1 (1.00)	0.0494 (1.00)	0.67 (1.00)	0.0437 (1.00)
CACNG3	8 (4%)	215	0.974 (1.00)	0.0481 (1.00)	0.704 (1.00)	0.396 (1.00)	0.346 (1.00)	0.786 (1.00)	0.62 (1.00)	0.485 (1.00)	0.668 (1.00)	0.641 (1.00)	0.543 (1.00)
PCDHGA7	5 (2%)	218	0.825 (1.00)	0.514 (1.00)	0.327 (1.00)	0.128 (1.00)	0.525 (1.00)	0.3 (1.00)	1 (1.00)	0.673 (1.00)	0.116 (1.00)	1 (1.00)	0.723 (1.00)
CCBP2	10 (4%)	213	0.205 (1.00)	0.812 (1.00)	0.29 (1.00)	0.783 (1.00)	0.228 (1.00)	0.236 (1.00)	1 (1.00)	0.526 (1.00)	0.25 (1.00)	1 (1.00)	0.129 (1.00)
MAP2K4	11 (5%)	212	0.409 (1.00)	0.049 (1.00)	0.51 (1.00)	0.0452 (1.00)	0.386 (1.00)	0.694 (1.00)	0.403 (1.00)	0.761 (1.00)	0.685 (1.00)	0.67 (1.00)	0.402 (1.00)
PCDHGA9	6 (3%)	217	0.728 (1.00)	0.224 (1.00)	0.669 (1.00)	0.213 (1.00)	0.323 (1.00)	1 (1.00)	0.607 (1.00)	0.43 (1.00)	0.745 (1.00)	0.107 (1.00)	0.827 (1.00)
RBM10	8 (4%)	215	0.0164 (1.00)	0.498 (1.00)	0.254 (1.00)	0.0239 (1.00)	0.15 (1.00)	0.0432 (1.00)	0.0107 (1.00)	0.157 (1.00)	0.282 (1.00)	1 (1.00)	0.00968 (1.00)
PTEN	7 (3%)	216	0.821 (1.00)	0.00791 (1.00)	0.679 (1.00)	0.166 (1.00)	0.175 (1.00)	1 (1.00)	1 (1.00)	0.713 (1.00)	0.224 (1.00)	0.597 (1.00)	0.51 (1.00)
DNMT1	17 (8%)	206	0.754 (1.00)	0.804 (1.00)	1 (1.00)	0.336 (1.00)	0.0876 (1.00)	0.435 (1.00)	1 (1.00)	0.207 (1.00)	0.0643 (1.00)	0.388 (1.00)	0.172 (1.00)
BCOR	9 (4%)	214	0.132 (1.00)	0.399 (1.00)	1 (1.00)	0.0641 (1.00)	0.0263 (1.00)	0.803 (1.00)	0.634 (1.00)	0.318 (1.00)	0.419 (1.00)	0.398 (1.00)	0.858 (1.00)
PCDHGB5	7 (3%)	216	0.0774 (1.00)	0.807 (1.00)	0.442 (1.00)	0.00488 (1.00)	0.0155 (1.00)	0.119 (1.00)	1 (1.00)	0.448 (1.00)	0.48 (1.00)	0.0566 (1.00)	0.0357 (1.00)
ZFP3	8 (4%)	215	0.216 (1.00)	0.48 (1.00)	1 (1.00)	0.224 (1.00)	0.256 (1.00)	0.421 (1.00)	0.61 (1.00)	0.485 (1.00)	1 (1.00)	0.634 (1.00)	0.224 (1.00)
RWDD2B	7 (3%)	216	0.895 (1.00)	0.18 (1.00)	1 (1.00)	0.351 (1.00)	0.174 (1.00)	0.117 (1.00)	0.607 (1.00)	0.713 (1.00)	1 (1.00)	1 (1.00)	0.0357 (1.00)
TBC1D10C	3 (1%)	220	0.548 (1.00)	0.375 (1.00)	0.554 (1.00)	0.281 (1.00)	0.701 (1.00)	0.133 (1.00)	1 (1.00)	0.609 (1.00)	0.0758 (1.00)	1 (1.00)	0.54 (1.00)
ERCC6L	5 (2%)	218	0.722 (1.00)	0.0726 (1.00)	1 (1.00)	0.424 (1.00)	0.199 (1.00)	0.387 (1.00)	1 (1.00)	0.0242 (1.00)	0.682 (1.00)	1 (1.00)	0.489 (1.00)
ERBB3	14 (6%)	209	0.512 (1.00)	0.519 (1.00)	0.558 (1.00)	0.0319 (1.00)	0.746 (1.00)	0.86 (1.00)	0.717 (1.00)	1 (1.00)	0.578 (1.00)	1 (1.00)	0.886 (1.00)
KLK2	3 (1%)	220	0.451 (1.00)	0.215 (1.00)	0.554 (1.00)	0.644 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.377 (1.00)	1 (1.00)	0.838 (1.00)
TAPBP	5 (2%)	218	0.357 (1.00)	0.286 (1.00)	0.644 (1.00)	0.29 (1.00)	0.0174 (1.00)	0.695 (1.00)	1 (1.00)	0.197 (1.00)	0.562 (1.00)	1 (1.00)	0.294 (1.00)
ERBB2	9 (4%)	214	0.478 (1.00)	0.307 (1.00)	0.462 (1.00)	0.479 (1.00)	0.345 (1.00)	0.71 (1.00)	1 (1.00)	0.0367 (1.00)	0.26 (1.00)	1 (1.00)	0.332 (1.00)
MORC2	5 (2%)	218	0.416 (1.00)	0.291 (1.00)	0.644 (1.00)	0.297 (1.00)	0.158 (1.00)	0.478 (1.00)	1 (1.00)	0.673 (1.00)	0.831 (1.00)	1 (1.00)	0.914 (1.00)
ABCA8	12 (5%)	211	0.725 (1.00)	0.938 (1.00)	1 (1.00)	0.0466 (1.00)	0.32 (1.00)	0.101 (1.00)	1 (1.00)	0.558 (1.00)	0.0252 (1.00)	0.665 (1.00)	0.315 (1.00)
SETD2	13 (6%)	210	0.996 (1.00)	0.975 (1.00)	0.759 (1.00)	0.555 (1.00)	0.0951 (1.00)	0.854 (1.00)	0.717 (1.00)	1 (1.00)	0.894 (1.00)	1 (1.00)	0.436 (1.00)

'TP53 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 0.00024 (Fisher's exact test), Q value = 0.12

Table S1. Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #9: 'HISTOLOGICAL.TYPE'

nPatients	COLON ADENOCARCINOMA	COLON MUCINOUS ADENOCARCINOMA	RECTAL ADENOCARCINOMA	RECTAL MUCINOUS ADENOCARCINOMA
ALL	130	22	57	8
TP53 MUTATED	67	4	40	4
TP53 WILD-TYPE	63	18	17	4

Figure S1. Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #9: 'HISTOLOGICAL.TYPE'

'BRAF MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 1e-05 (Fisher's exact test), Q value = 0.0051

Table S2. Gene #12: 'BRAF MUTATION STATUS' versus Clinical Feature #9: 'HISTOLOGICAL.TYPE'

nPatients	COLON ADENOCARCINOMA	COLON MUCINOUS ADENOCARCINOMA	RECTAL ADENOCARCINOMA	RECTAL MUCINOUS ADENOCARCINOMA
ALL	130	22	57	8
BRAF MUTATED	10	10	0	1
BRAF WILD-TYPE	120	12	57	7

Figure S2. Get High-res Image Gene #12: 'BRAF MUTATION STATUS' versus Clinical Feature #9: 'HISTOLOGICAL.TYPE'

'PCDHA3 MUTATION STATUS' versus 'NEOPLASM.DISEASESTAGE'

P value = 1e-05 (Fisher's exact test), Q value = 0.0051

Table S3. Gene #20: 'PCDHA3 MUTATION STATUS' versus Clinical Feature #4: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE IIA	STAGE IIB	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV	STAGE IVA
ALL	49	20	57	4	18	2	20	20	31	1
PCDHA3 MUTATED	0	2	0	4	2	0	0	1	2	0
PCDHA3 WILD-TYPE	49	18	57	0	16	2	20	19	29	1

Figure S3. Get High-res Image Gene #20: 'PCDHA3 MUTATION STATUS' versus Clinical Feature #4: 'NEOPLASM.DISEASESTAGE'

'ESR1 MUTATION STATUS' versus 'NEOPLASM.DISEASESTAGE'

P value = 6e-05 (Fisher's exact test), Q value = 0.03

Table S4. Gene #46: 'ESR1 MUTATION STATUS' versus Clinical Feature #4: 'NEOPLASM.DISEASESTAGE'

nPatients	STAGE I	STAGE II	STAGE IIA	STAGE IIB	STAGE III	STAGE IIIA	STAGE IIIB	STAGE IIIC	STAGE IV	STAGE IVA
ALL	49	20	57	4	18	2	20	20	31	1
ESR1 MUTATED	1	2	0	3	0	0	3	1	0	0
ESR1 WILD-TYPE	48	18	57	1	18	2	17	19	31	1

Figure S4. Get High-res Image Gene #46: 'ESR1 MUTATION STATUS' versus Clinical Feature #4: 'NEOPLASM.DISEASESTAGE'

Methods & Data

Input

Mutation data file = transformed.cor.cli.txt
Clinical data file = COADREAD-TP.merged_data.txt
Number of patients = 223
Number of significantly mutated genes = 46
Number of selected clinical features = 11
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

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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References

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

[2] 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)

[3] 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)

Made with Nozzle