Correlation between gene mutation status and selected clinical features

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 12 clinical features across 194 patients, 10 significant findings detected with Q value < 0.25.

TP53 mutation correlated to 'GENDER' and 'RACE'.
CTNNB1 mutation correlated to 'GENDER'.
RB1 mutation correlated to 'YEARS_TO_BIRTH' and 'RACE'.
ARID1A mutation correlated to 'Time to Death'.
BAP1 mutation correlated to 'GENDER'.
ALB mutation correlated to 'RACE'.
IL6ST mutation correlated to 'Time to Death'.
HIST1H1C mutation correlated to 'PATHOLOGY_T_STAGE'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 20 genes and 12 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	YEARS TO BIRTH	PATHOLOGIC STAGE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	PATHOLOGY M STAGE	GENDER	RADIATION THERAPY	HISTOLOGICAL TYPE	RESIDUAL TUMOR	RACE	ETHNICITY
	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	Fisher's exact test	Fisher's exact test
TP53	61 (31%)	133	0.0849 (0.719)	0.087 (0.719)	0.396 (1.00)	0.179 (0.86)	0.559 (1.00)	0.308 (1.00)	0.00202 (0.114)	1 (1.00)	0.693 (1.00)	0.96 (1.00)	5e-05 (0.006)	0.179 (0.86)
RB1	15 (8%)	179	0.608 (1.00)	0.00267 (0.114)	0.455 (1.00)	0.178 (0.86)	1 (1.00)	1 (1.00)	0.404 (1.00)	1 (1.00)	1 (1.00)	0.528 (1.00)	0.00687 (0.206)	0.358 (1.00)
CTNNB1	50 (26%)	144	0.981 (1.00)	0.208 (0.887)	0.75 (1.00)	0.598 (1.00)	0.161 (0.86)	1 (1.00)	3.08e-05 (0.006)	0.173 (0.86)	0.681 (1.00)	0.117 (0.799)	0.293 (1.00)	1 (1.00)
ARID1A	17 (9%)	177	0.00957 (0.23)	0.198 (0.887)	0.189 (0.872)	0.633 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.22 (0.9)	1 (1.00)	0.297 (1.00)	0.415 (1.00)	1 (1.00)
BAP1	11 (6%)	183	0.237 (0.912)	0.712 (1.00)	0.0478 (0.603)	0.072 (0.709)	0.181 (0.86)	0.227 (0.9)	0.000161 (0.0129)	1 (1.00)	1 (1.00)	0.642 (1.00)	0.898 (1.00)	1 (1.00)
ALB	18 (9%)	176	0.541 (1.00)	0.028 (0.517)	0.241 (0.912)	0.113 (0.799)	0.243 (0.912)	1 (1.00)	0.0356 (0.57)	1 (1.00)	1 (1.00)	0.403 (1.00)	0.00863 (0.23)	1 (1.00)
IL6ST	7 (4%)	187	0.00285 (0.114)	0.17 (0.86)	0.954 (1.00)	0.867 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.115 (0.799)	1 (1.00)	0.687 (1.00)	0.824 (1.00)	1 (1.00)
HIST1H1C	5 (3%)	189	0.171 (0.86)	0.88 (1.00)	0.0434 (0.603)	0.00484 (0.166)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.0991 (0.743)	0.318 (1.00)	0.0226 (0.452)	1 (1.00)
AXIN1	9 (5%)	185	0.0321 (0.551)	0.799 (1.00)	0.0929 (0.719)	0.63 (1.00)	1 (1.00)	0.18 (0.86)	1 (1.00)	1 (1.00)	1 (1.00)	0.296 (1.00)	1 (1.00)	0.206 (0.887)
TSC2	9 (5%)	185	0.989 (1.00)	0.515 (1.00)	0.179 (0.86)	0.0768 (0.709)	1 (1.00)	1 (1.00)	0.723 (1.00)	1 (1.00)	1 (1.00)	0.549 (1.00)	0.211 (0.887)	0.183 (0.86)
APOB	24 (12%)	170	0.768 (1.00)	0.543 (1.00)	0.0615 (0.671)	0.776 (1.00)	0.375 (1.00)	0.413 (1.00)	0.503 (1.00)	1 (1.00)	1 (1.00)	0.683 (1.00)	0.0765 (0.709)	1 (1.00)
PTEN	7 (4%)	187	0.341 (1.00)	0.26 (0.945)	0.85 (1.00)	0.759 (1.00)	1 (1.00)	1 (1.00)	0.425 (1.00)	1 (1.00)	1 (1.00)	0.2 (0.887)	0.457 (1.00)	0.158 (0.86)
EEF1A1	5 (3%)	189	0.0392 (0.588)	0.326 (1.00)	0.669 (1.00)	0.386 (1.00)	1 (1.00)	1 (1.00)	0.163 (0.86)	1 (1.00)	1 (1.00)	0.561 (1.00)	0.178 (0.86)	1 (1.00)
KIF19	10 (5%)	184	0.0916 (0.719)	0.0452 (0.603)	0.918 (1.00)	0.64 (1.00)	1 (1.00)	1 (1.00)	0.499 (1.00)	0.161 (0.86)	1 (1.00)	0.596 (1.00)	0.506 (1.00)	1 (1.00)
THADA	6 (3%)	188	0.695 (1.00)	0.0584 (0.667)	0.919 (1.00)	0.53 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.12 (0.799)	0.0928 (0.719)	0.303 (1.00)	1 (1.00)
PRKDC	11 (6%)	183	0.0169 (0.369)	0.987 (1.00)	0.434 (1.00)	0.328 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
HNF1A	8 (4%)	186	0.674 (1.00)	0.403 (1.00)	0.229 (0.9)	0.281 (0.993)	1 (1.00)	1 (1.00)	0.458 (1.00)	1 (1.00)	1 (1.00)	0.247 (0.913)	0.689 (1.00)	1 (1.00)
F5	4 (2%)	190	0.844 (1.00)	0.225 (0.9)	0.624 (1.00)	0.443 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.0503 (0.603)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)
GNAS	7 (4%)	187	0.266 (0.951)	0.975 (1.00)	0.686 (1.00)	0.316 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.689 (1.00)	1 (1.00)
MLL4	10 (5%)	184	0.986 (1.00)	0.935 (1.00)	0.976 (1.00)	0.956 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.0721 (0.709)	1 (1.00)

'TP53 MUTATION STATUS' versus 'GENDER'

P value = 0.00202 (Fisher's exact test), Q value = 0.11

Table S1. Gene #1: 'TP53 MUTATION STATUS' versus Clinical Feature #7: 'GENDER'

nPatients	FEMALE	MALE
ALL	69	125
TP53 MUTATED	12	49
TP53 WILD-TYPE	57	76

Figure S1. Get High-res Image Gene #1: 'TP53 MUTATION STATUS' versus Clinical Feature #7: 'GENDER'

'TP53 MUTATION STATUS' versus 'RACE'

P value = 5e-05 (Fisher's exact test), Q value = 0.006

Table S2. Gene #1: 'TP53 MUTATION STATUS' versus Clinical Feature #11: 'RACE'

nPatients	AMERICAN INDIAN OR ALASKA NATIVE	ASIAN	BLACK OR AFRICAN AMERICAN	WHITE
ALL	1	54	14	117
TP53 MUTATED	1	23	10	25
TP53 WILD-TYPE	0	31	4	92

Figure S2. Get High-res Image Gene #1: 'TP53 MUTATION STATUS' versus Clinical Feature #11: 'RACE'

'CTNNB1 MUTATION STATUS' versus 'GENDER'

P value = 3.08e-05 (Fisher's exact test), Q value = 0.006

Table S3. Gene #2: 'CTNNB1 MUTATION STATUS' versus Clinical Feature #7: 'GENDER'

nPatients	FEMALE	MALE
ALL	69	125
CTNNB1 MUTATED	6	44
CTNNB1 WILD-TYPE	63	81

Figure S3. Get High-res Image Gene #2: 'CTNNB1 MUTATION STATUS' versus Clinical Feature #7: 'GENDER'

'RB1 MUTATION STATUS' versus 'YEARS_TO_BIRTH'

P value = 0.00267 (Wilcoxon-test), Q value = 0.11

Table S4. Gene #3: 'RB1 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

	nPatients	Mean (Std.Dev)
ALL	192	60.1 (13.9)
RB1 MUTATED	15	51.8 (11.3)
RB1 WILD-TYPE	177	60.8 (13.9)

Figure S4. Get High-res Image Gene #3: 'RB1 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'RB1 MUTATION STATUS' versus 'RACE'

P value = 0.00687 (Fisher's exact test), Q value = 0.21

Table S5. Gene #3: 'RB1 MUTATION STATUS' versus Clinical Feature #11: 'RACE'

nPatients	AMERICAN INDIAN OR ALASKA NATIVE	ASIAN	BLACK OR AFRICAN AMERICAN	WHITE
ALL	1	54	14	117
RB1 MUTATED	0	10	1	4
RB1 WILD-TYPE	1	44	13	113

Figure S5. Get High-res Image Gene #3: 'RB1 MUTATION STATUS' versus Clinical Feature #11: 'RACE'

'ARID1A MUTATION STATUS' versus 'Time to Death'

P value = 0.00957 (logrank test), Q value = 0.23

Table S6. Gene #4: 'ARID1A MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	192	88	0.0 - 114.3 (19.3)
ARID1A MUTATED	16	11	0.3 - 60.9 (13.6)
ARID1A WILD-TYPE	176	77	0.0 - 114.3 (19.6)

Figure S6. Get High-res Image Gene #4: 'ARID1A MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'BAP1 MUTATION STATUS' versus 'GENDER'

P value = 0.000161 (Fisher's exact test), Q value = 0.013

Table S7. Gene #6: 'BAP1 MUTATION STATUS' versus Clinical Feature #7: 'GENDER'

nPatients	FEMALE	MALE
ALL	69	125
BAP1 MUTATED	10	1
BAP1 WILD-TYPE	59	124

Figure S7. Get High-res Image Gene #6: 'BAP1 MUTATION STATUS' versus Clinical Feature #7: 'GENDER'

'ALB MUTATION STATUS' versus 'RACE'

P value = 0.00863 (Fisher's exact test), Q value = 0.23

Table S8. Gene #7: 'ALB MUTATION STATUS' versus Clinical Feature #11: 'RACE'

nPatients	AMERICAN INDIAN OR ALASKA NATIVE	ASIAN	BLACK OR AFRICAN AMERICAN	WHITE
ALL	1	54	14	117
ALB MUTATED	1	1	1	15
ALB WILD-TYPE	0	53	13	102

Figure S8. Get High-res Image Gene #7: 'ALB MUTATION STATUS' versus Clinical Feature #11: 'RACE'

'IL6ST MUTATION STATUS' versus 'Time to Death'

P value = 0.00285 (logrank test), Q value = 0.11

Table S9. Gene #9: 'IL6ST MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

	nPatients	nDeath	Duration Range (Median), Month
ALL	192	88	0.0 - 114.3 (19.3)
IL6ST MUTATED	7	0	7.2 - 113.0 (56.2)
IL6ST WILD-TYPE	185	88	0.0 - 114.3 (19.0)

Figure S9. Get High-res Image Gene #9: 'IL6ST MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'HIST1H1C MUTATION STATUS' versus 'PATHOLOGY_T_STAGE'

P value = 0.00484 (Fisher's exact test), Q value = 0.17

Table S10. Gene #20: 'HIST1H1C MUTATION STATUS' versus Clinical Feature #4: 'PATHOLOGY_T_STAGE'

nPatients	T1	T2	T3	T4
ALL	79	50	52	11
HIST1H1C MUTATED	0	4	0	1
HIST1H1C WILD-TYPE	79	46	52	10

Figure S10. Get High-res Image Gene #20: 'HIST1H1C MUTATION STATUS' versus Clinical Feature #4: 'PATHOLOGY_T_STAGE'

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/LIHC-TP/19897751/transformed.cor.cli.txt
Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/LIHC-TP/19775332/LIHC-TP.merged_data.txt
Number of patients = 194
Number of significantly mutated genes = 20
Number of selected clinical features = 12
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.

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