Correlation between gene mutation status and selected clinical features

Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (Primary solid tumor)

28 January 2016 | analyses__2016_01_28

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 (2016): Correlation between gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1JM290Q

Overview

Introduction

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

Summary

Testing the association between mutation status of 20 genes and 39 clinical features across 194 patients, 2 significant findings detected with Q value < 0.25.

PIK3CA mutation correlated to 'YEARS_TO_BIRTH' and 'AGE_AT_DIAGNOSIS'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 20 genes and 39 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 2 significant findings detected.


		Clinical Features	Time to Death	YEARS TO BIRTH	PATHOLOGY T STAGE	PATHOLOGY N STAGE	PATHOLOGY M STAGE	RADIATION THERAPY	HISTOLOGICAL TYPE	NUMBER PACK YEARS SMOKED	NUMBER OF LYMPH NODES	RACE	ETHNICITY	WEIGHT KG AT DIAGNOSIS	TUMOR STATUS	NEOPLASM HISTOLOGIC GRADE	TOBACCO SMOKING YEAR STOPPED	TOBACCO SMOKING PACK YEARS SMOKED	TOBACCO SMOKING HISTORY	AGEBEGANSMOKINGINYEARS	RADIATION THERAPY STATUS	PREGNANCIES COUNT TOTAL	PREGNANCIES COUNT STILLBIRTH	PREGNANCY SPONTANEOUS ABORTION COUNT	PREGNANCIES COUNT LIVE BIRTH	PREGNANCY THERAPEUTIC ABORTION COUNT	PREGNANCIES COUNT ECTOPIC	POS LYMPH NODE LOCATION	MENOPAUSE STATUS	LYMPHOVASCULAR INVOLVEMENT	LYMPH NODES EXAMINED HE COUNT	LYMPH NODES EXAMINED	KERATINIZATION SQUAMOUS CELL	INITIAL PATHOLOGIC DX YEAR	HISTORY HORMONAL CONTRACEPTIVES USE	HEIGHT CM AT DIAGNOSIS	CORPUS INVOLVEMENT	CHEMO CONCURRENT TYPE	CERVIX SUV RESULTS	AGE AT DIAGNOSIS	CLINICAL STAGE
	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	Wilcoxon-test	Wilcoxon-test	Fisher's exact test	Fisher's exact test	Wilcoxon-test	Fisher's exact test	Fisher's exact test	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Fisher's exact test	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Wilcoxon-test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Wilcoxon-test	Wilcoxon-test	Fisher's exact test	Wilcoxon-test	Fisher's exact test	Wilcoxon-test	Fisher's exact test	Fisher's exact test	Wilcoxon-test	Wilcoxon-test	Fisher's exact test
PIK3CA	53 (27%)	141	0.643 (1.00)	0.000461 (0.18)	0.185 (1.00)	0.541 (1.00)	0.264 (1.00)	0.819 (1.00)	0.643 (1.00)	0.102 (0.927)	0.421 (1.00)	0.0792 (0.897)	0.00185 (0.263)	0.776 (1.00)	0.564 (1.00)	0.086 (0.927)	0.903 (1.00)	0.102 (0.927)	0.329 (1.00)	0.584 (1.00)	0.515 (1.00)	0.702 (1.00)	0.863 (1.00)	0.938 (1.00)	0.884 (1.00)	0.243 (1.00)	0.502 (1.00)	0.365 (1.00)	0.00707 (0.501)	0.684 (1.00)	0.421 (1.00)	0.917 (1.00)	0.513 (1.00)	0.815 (1.00)	0.935 (1.00)	0.0596 (0.86)	0.351 (1.00)	0.0839 (0.921)	0.915 (1.00)	0.000334 (0.18)	0.33 (1.00)
PTEN	15 (8%)	179	0.222 (1.00)	0.00549 (0.501)	0.22 (1.00)	0.725 (1.00)	0.264 (1.00)	0.228 (1.00)	0.474 (1.00)	0.412 (1.00)	0.553 (1.00)	0.52 (1.00)	1 (1.00)	0.691 (1.00)	1 (1.00)	0.632 (1.00)	0.943 (1.00)	0.412 (1.00)	0.33 (1.00)	0.281 (1.00)	1 (1.00)	0.621 (1.00)	0.028 (0.732)	0.191 (1.00)	0.587 (1.00)	0.34 (1.00)	0.9 (1.00)	0.245 (1.00)	0.202 (1.00)	1 (1.00)	0.553 (1.00)	0.719 (1.00)	1 (1.00)	0.861 (1.00)	0.309 (1.00)	0.729 (1.00)	0.03 (0.745)	0.0541 (0.86)		0.0062 (0.501)	0.181 (1.00)
HLA-B	11 (6%)	183	0.487 (1.00)	0.322 (1.00)	0.102 (0.927)	1 (1.00)	1 (1.00)	0.695 (1.00)	0.745 (1.00)	0.309 (1.00)	0.73 (1.00)	0.0683 (0.86)	0.0113 (0.552)	0.554 (1.00)	0.732 (1.00)	0.0595 (0.86)	0.857 (1.00)	0.309 (1.00)	0.415 (1.00)	0.043 (0.86)	1 (1.00)	0.0417 (0.86)	0.441 (1.00)	0.0647 (0.86)	0.342 (1.00)	0.0242 (0.732)	0.9 (1.00)		0.542 (1.00)	1 (1.00)	0.73 (1.00)	0.881 (1.00)	0.665 (1.00)	0.969 (1.00)	0.787 (1.00)	0.2 (1.00)	0.574 (1.00)	1 (1.00)		0.346 (1.00)	0.069 (0.86)
HLA-A	16 (8%)	178	0.288 (1.00)	0.231 (1.00)	0.149 (1.00)	0.0305 (0.745)	1 (1.00)	1 (1.00)	0.717 (1.00)	0.0527 (0.86)	0.0592 (0.86)	0.546 (1.00)	0.351 (1.00)	0.681 (1.00)	0.364 (1.00)	0.0107 (0.552)	0.259 (1.00)	0.0527 (0.86)	0.549 (1.00)	0.874 (1.00)	1 (1.00)	0.323 (1.00)	0.588 (1.00)	0.201 (1.00)	0.434 (1.00)	0.317 (1.00)	0.991 (1.00)	0.503 (1.00)	0.541 (1.00)	0.712 (1.00)	0.0592 (0.86)	0.335 (1.00)	0.738 (1.00)	0.301 (1.00)	1 (1.00)	0.288 (1.00)	0.293 (1.00)	1 (1.00)		0.144 (1.00)	0.235 (1.00)
KRAS	11 (6%)	183	0.514 (1.00)	0.836 (1.00)	0.197 (1.00)	1 (1.00)	0.182 (1.00)	1 (1.00)	0.00147 (0.263)	0.347 (1.00)	0.979 (1.00)	0.449 (1.00)	1 (1.00)	0.455 (1.00)	0.141 (1.00)	0.627 (1.00)		0.347 (1.00)	0.67 (1.00)	0.57 (1.00)	1 (1.00)	0.099 (0.927)	0.579 (1.00)	0.566 (1.00)	0.631 (1.00)	0.359 (1.00)	0.464 (1.00)	1 (1.00)	0.529 (1.00)	0.089 (0.927)	0.979 (1.00)	0.202 (1.00)	0.528 (1.00)	0.884 (1.00)	0.366 (1.00)	0.691 (1.00)	1 (1.00)	0.0172 (0.732)		0.795 (1.00)	0.816 (1.00)
MLL2	22 (11%)	172	0.05 (0.86)	0.178 (1.00)	0.87 (1.00)	0.766 (1.00)	1 (1.00)	0.542 (1.00)	0.92 (1.00)	0.643 (1.00)	0.296 (1.00)	0.705 (1.00)	0.663 (1.00)	0.786 (1.00)	0.785 (1.00)	0.9 (1.00)		0.643 (1.00)	0.506 (1.00)	0.779 (1.00)	1 (1.00)	0.538 (1.00)	0.795 (1.00)	0.188 (1.00)	0.463 (1.00)	0.996 (1.00)	0.869 (1.00)	0.142 (1.00)	0.8 (1.00)	0.158 (1.00)	0.296 (1.00)	0.8 (1.00)	0.774 (1.00)	0.595 (1.00)	0.658 (1.00)	0.22 (1.00)	0.0277 (0.732)	1 (1.00)		0.195 (1.00)	0.226 (1.00)
FBXW7	19 (10%)	175	0.76 (1.00)	0.415 (1.00)	0.0706 (0.86)	0.137 (1.00)	1 (1.00)	1 (1.00)	0.655 (1.00)	0.988 (1.00)	0.159 (1.00)	0.919 (1.00)	0.648 (1.00)	0.718 (1.00)	0.257 (1.00)	0.691 (1.00)	0.409 (1.00)	0.988 (1.00)	0.415 (1.00)	0.581 (1.00)	1 (1.00)	0.495 (1.00)	0.513 (1.00)	0.215 (1.00)	0.283 (1.00)	0.503 (1.00)	0.264 (1.00)	0.161 (1.00)	0.741 (1.00)	0.787 (1.00)	0.159 (1.00)	0.374 (1.00)	1 (1.00)	0.639 (1.00)	0.458 (1.00)	0.203 (1.00)	1 (1.00)	0.434 (1.00)		0.381 (1.00)	0.455 (1.00)
EP300	21 (11%)	173	0.702 (1.00)	0.0241 (0.732)	0.283 (1.00)	0.277 (1.00)	1 (1.00)	0.495 (1.00)	0.771 (1.00)	0.91 (1.00)	0.401 (1.00)	0.631 (1.00)	0.694 (1.00)	0.542 (1.00)	1 (1.00)	0.834 (1.00)		0.91 (1.00)	0.341 (1.00)	0.185 (1.00)	1 (1.00)	0.525 (1.00)	0.729 (1.00)	0.323 (1.00)	0.116 (0.985)	0.93 (1.00)	0.233 (1.00)	0.217 (1.00)	0.17 (1.00)	0.78 (1.00)	0.401 (1.00)	0.721 (1.00)	0.553 (1.00)	0.903 (1.00)	0.276 (1.00)	0.64 (1.00)	0.65 (1.00)	1 (1.00)		0.0278 (0.732)	0.021 (0.732)
MAPK1	9 (5%)	185	0.0975 (0.927)	0.179 (1.00)	0.409 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.812 (1.00)	0.179 (1.00)	0.658 (1.00)	1 (1.00)	0.555 (1.00)	0.505 (1.00)	0.457 (1.00)	0.245 (1.00)		0.179 (1.00)	0.525 (1.00)	0.222 (1.00)	1 (1.00)	0.62 (1.00)	0.503 (1.00)	0.349 (1.00)	0.732 (1.00)	0.188 (1.00)	0.378 (1.00)		0.473 (1.00)	0.155 (1.00)	0.658 (1.00)	0.76 (1.00)	0.676 (1.00)	0.948 (1.00)	1 (1.00)	0.22 (1.00)	0.293 (1.00)			0.19 (1.00)	0.352 (1.00)
MLL3	29 (15%)	165	0.0661 (0.86)	0.157 (1.00)	0.418 (1.00)	0.775 (1.00)	1 (1.00)	0.256 (1.00)	0.98 (1.00)	0.713 (1.00)	0.73 (1.00)	0.0474 (0.86)	0.404 (1.00)	0.629 (1.00)	0.0716 (0.86)	0.803 (1.00)	0.413 (1.00)	0.713 (1.00)	0.269 (1.00)	0.753 (1.00)	1 (1.00)	0.486 (1.00)	0.916 (1.00)	0.714 (1.00)	0.764 (1.00)	0.187 (1.00)	0.566 (1.00)	0.893 (1.00)	0.127 (1.00)	0.439 (1.00)	0.73 (1.00)	0.741 (1.00)	0.78 (1.00)	0.0481 (0.86)	0.327 (1.00)	0.868 (1.00)	1 (1.00)	1 (1.00)		0.171 (1.00)	0.435 (1.00)
ARID1A	14 (7%)	180	0.589 (1.00)	0.163 (1.00)	0.00231 (0.263)	1 (1.00)	0.0446 (0.86)	0.695 (1.00)	0.0068 (0.501)		0.848 (1.00)	0.213 (1.00)	0.0216 (0.732)	0.84 (1.00)	0.523 (1.00)	0.382 (1.00)			0.0446 (0.86)		0.288 (1.00)	0.618 (1.00)	0.0349 (0.8)	0.551 (1.00)	0.0535 (0.86)	0.187 (1.00)	0.801 (1.00)		1 (1.00)	0.739 (1.00)	0.848 (1.00)	0.47 (1.00)	1 (1.00)	0.602 (1.00)	1 (1.00)	0.319 (1.00)	1 (1.00)	0.00977 (0.544)		0.176 (1.00)	0.0655 (0.86)
NFE2L2	12 (6%)	182	0.754 (1.00)	0.923 (1.00)	0.14 (1.00)	0.679 (1.00)	1 (1.00)	0.398 (1.00)	0.765 (1.00)	0.677 (1.00)	0.771 (1.00)	0.306 (1.00)	0.238 (1.00)	0.447 (1.00)	0.17 (1.00)	0.0821 (0.915)	0.59 (1.00)	0.677 (1.00)	0.0269 (0.732)	0.326 (1.00)	1 (1.00)	0.176 (1.00)	0.413 (1.00)	0.491 (1.00)	0.405 (1.00)	0.113 (0.969)	0.991 (1.00)	0.368 (1.00)	1 (1.00)	0.209 (1.00)	0.771 (1.00)	0.075 (0.886)	0.501 (1.00)	0.0557 (0.86)	0.842 (1.00)	0.768 (1.00)	0.23 (1.00)	1 (1.00)	0.82 (1.00)	0.956 (1.00)	0.0948 (0.927)
CASP8	9 (5%)	185	0.93 (1.00)	0.33 (1.00)	0.162 (1.00)	0.665 (1.00)	1 (1.00)	1 (1.00)	0.809 (1.00)	0.0908 (0.927)	0.707 (1.00)	0.899 (1.00)	0.453 (1.00)	0.921 (1.00)	0.457 (1.00)	0.192 (1.00)	0.615 (1.00)	0.0908 (0.927)	0.666 (1.00)	0.27 (1.00)	1 (1.00)	0.475 (1.00)	0.352 (1.00)	0.0945 (0.927)	0.164 (1.00)	0.181 (1.00)	0.378 (1.00)		0.694 (1.00)	0.12 (1.00)	0.707 (1.00)	0.805 (1.00)	0.647 (1.00)	0.251 (1.00)	0.474 (1.00)	0.907 (1.00)	0.397 (1.00)	1 (1.00)		0.346 (1.00)	0.235 (1.00)
FAT2	11 (6%)	183	0.425 (1.00)	0.155 (1.00)	0.533 (1.00)	1 (1.00)	1 (1.00)	0.383 (1.00)	0.281 (1.00)	0.0703 (0.86)	0.722 (1.00)	0.248 (1.00)	0.0991 (0.927)	0.376 (1.00)	0.455 (1.00)	0.0652 (0.86)		0.0703 (0.86)	0.976 (1.00)	0.143 (1.00)	1 (1.00)	0.254 (1.00)	0.539 (1.00)	0.444 (1.00)	0.246 (1.00)	0.613 (1.00)	0.574 (1.00)	0.35 (1.00)	0.559 (1.00)	0.681 (1.00)	0.722 (1.00)	0.863 (1.00)	0.665 (1.00)	0.778 (1.00)	0.786 (1.00)	0.00847 (0.517)	0.293 (1.00)	1 (1.00)		0.168 (1.00)	0.491 (1.00)
ZNF750	9 (5%)	185	0.949 (1.00)	0.772 (1.00)	0.528 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.51 (1.00)	0.179 (1.00)	0.227 (1.00)	0.056 (0.86)	0.201 (1.00)	0.0228 (0.732)	0.202 (1.00)	0.437 (1.00)		0.179 (1.00)	0.477 (1.00)	0.637 (1.00)	1 (1.00)	0.857 (1.00)	0.111 (0.962)	0.36 (1.00)	0.188 (1.00)	0.865 (1.00)	0.517 (1.00)		1 (1.00)	1 (1.00)	0.227 (1.00)	0.268 (1.00)	0.433 (1.00)	0.31 (1.00)	1 (1.00)	0.00236 (0.263)	0.168 (1.00)	1 (1.00)		0.901 (1.00)	0.658 (1.00)
C12ORF43	4 (2%)	190	0.185 (1.00)	0.564 (1.00)	0.0666 (0.86)	0.551 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)			0.491 (1.00)	1 (1.00)	0.364 (1.00)	0.574 (1.00)	1 (1.00)					0.2 (1.00)	0.209 (1.00)			0.58 (1.00)				0.662 (1.00)	0.497 (1.00)			1 (1.00)	0.198 (1.00)		0.98 (1.00)	0.0224 (0.732)			0.577 (1.00)	0.143 (1.00)
C3ORF70	4 (2%)	190	0.41 (1.00)	0.956 (1.00)	0.263 (1.00)	0.551 (1.00)	1 (1.00)	1 (1.00)	0.565 (1.00)			0.671 (1.00)	0.329 (1.00)	0.485 (1.00)	1 (1.00)	0.0504 (0.86)			0.967 (1.00)			0.0321 (0.759)			0.098 (0.927)				1 (1.00)	0.62 (1.00)			1 (1.00)	0.196 (1.00)		0.537 (1.00)	0.111 (0.962)			0.978 (1.00)	0.109 (0.962)
BAP1	4 (2%)	190	0.606 (1.00)	0.672 (1.00)		0.0986 (0.927)	1 (1.00)		1 (1.00)			0.384 (1.00)	1 (1.00)	0.671 (1.00)	0.574 (1.00)	1 (1.00)			0.407 (1.00)		1 (1.00)	0.679 (1.00)			0.792 (1.00)					1 (1.00)		0.522 (1.00)	1 (1.00)	0.916 (1.00)		0.00207 (0.263)	0.285 (1.00)			0.662 (1.00)	0.587 (1.00)
USP28	4 (2%)	190	0.865 (1.00)	0.0201 (0.732)	0.603 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.111 (0.962)		0.797 (1.00)	1 (1.00)	1 (1.00)	0.285 (1.00)	1 (1.00)	0.61 (1.00)			0.645 (1.00)			0.577 (1.00)	0.0479 (0.86)	0.55 (1.00)	0.544 (1.00)	0.209 (1.00)	0.579 (1.00)		0.0972 (0.927)	0.497 (1.00)	0.797 (1.00)	0.829 (1.00)	0.528 (1.00)	0.0794 (0.897)	1 (1.00)	0.364 (1.00)	1 (1.00)	1 (1.00)		0.0209 (0.732)	1 (1.00)
IFNGR1	6 (3%)	188	0.433 (1.00)	0.612 (1.00)	0.0281 (0.732)	0.534 (1.00)	1 (1.00)	0.578 (1.00)	0.254 (1.00)		0.347 (1.00)	0.306 (1.00)	0.453 (1.00)	0.0762 (0.887)	1 (1.00)	0.736 (1.00)			0.95 (1.00)		1 (1.00)	0.00861 (0.517)	0.579 (1.00)	0.178 (1.00)	0.0646 (0.86)	0.256 (1.00)	0.446 (1.00)		0.601 (1.00)	0.245 (1.00)	0.347 (1.00)	0.252 (1.00)	0.551 (1.00)	0.778 (1.00)	1 (1.00)	0.866 (1.00)	0.397 (1.00)			0.636 (1.00)	0.473 (1.00)

'PIK3CA MUTATION STATUS' versus 'YEARS_TO_BIRTH'

P value = 0.000461 (Wilcoxon-test), Q value = 0.18

Table S1. Gene #12: 'PIK3CA MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	192	47.3 (13.2)
PIK3CA MUTATED	52	53.4 (13.8)
PIK3CA WILD-TYPE	140	45.0 (12.3)

Figure S1. Get High-res Image Gene #12: 'PIK3CA MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'PIK3CA MUTATION STATUS' versus 'AGE_AT_DIAGNOSIS'

P value = 0.000334 (Wilcoxon-test), Q value = 0.18

Table S2. Gene #12: 'PIK3CA MUTATION STATUS' versus Clinical Feature #38: 'AGE_AT_DIAGNOSIS'

	nPatients	Mean (Std.Dev)
ALL	194	47.4 (13.2)
PIK3CA MUTATED	53	53.5 (13.8)
PIK3CA WILD-TYPE	141	45.1 (12.3)

Figure S2. Get High-res Image Gene #12: 'PIK3CA MUTATION STATUS' versus Clinical Feature #38: 'AGE_AT_DIAGNOSIS'

Methods & Data

Input

Mutation data file = sample_sig_gene_table.txt from Mutsig_2CV pipeline
Processed Mutation data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_Correlate_Genomic_Events_Preprocess/CESC-TP/22574677/transformed.cor.cli.txt
Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/CESC-TP/22489370/CESC-TP.merged_data.txt
Number of patients = 194
Number of significantly mutated genes = 20
Number of selected clinical features = 39
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)

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