Correlation between gene mutation status and selected clinical features

Lung Adenocarcinoma (Primary solid tumor)

17 April 2019 | None

Maintainer Information

Maintained by Broad Institute GDAC (Broad Institute of MIT & Harvard)

Overview

Introduction

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

Summary

Testing the association between mutation status of 19 genes and 17 clinical features across 108 patients, no significant finding detected with Q value < 0.25.

No gene mutations related to clinical features.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 19 genes and 17 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, no significant finding detected.


		Clinical Features	DAYS TO DEATH OR LAST FUP	HISTOLOGICAL TYPE	HISTOLOGIC GRADE	KARNOFSKY PERFORMANCE SCORE	PATHOLOGY T STAGE	PATHOLOGY N STAGE	PATHOLOGIC STAGE	YEARS TO BIRTH	ETHNICITY	GENDER	RACE	RADIATION THERAPY	BMI	NUMBER PACK YEARS SMOKED	SMOKER	COUNTRY OF ORIGIN	ORIGIN ASIA
	nMutated (%)	nWild-Type	logrank test	Fisher's exact test	Fisher's exact test	Wilcoxon-test	Fisher's exact test	Fisher's exact test	Fisher's exact 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	Fisher's exact test	Fisher's exact test	Fisher's exact test
TP53	59 (55%)	49	0.578 (1.00)	0.0181 (0.604)	0.153 (0.835)	0.185 (0.91)	0.596 (1.00)	0.101 (0.795)	0.946 (1.00)	0.16 (0.835)	0.536 (1.00)	0.542 (1.00)	1 (1.00)	0.141 (0.827)	0.246 (0.982)	0.227 (0.954)	1 (1.00)	0.0543 (0.677)	0.0187 (0.604)
KRAS	34 (31%)	74	0.153 (0.835)	0.0591 (0.677)	0.796 (1.00)	0.227 (0.954)	0.136 (0.827)	0.614 (1.00)	0.135 (0.827)	0.892 (1.00)	0.536 (1.00)	0.0272 (0.604)	0.764 (1.00)	0.796 (1.00)	0.0206 (0.604)	0.851 (1.00)	0.0611 (0.677)	0.0434 (0.677)	0.527 (1.00)
STK11	20 (19%)	88	0.251 (0.982)	0.617 (1.00)	0.866 (1.00)	0.306 (0.982)	0.118 (0.805)	0.304 (0.982)	0.385 (1.00)	0.669 (1.00)	1 (1.00)	0.0673 (0.677)	0.497 (1.00)	0.36 (1.00)	0.307 (0.982)	0.465 (1.00)	0.464 (1.00)	0.114 (0.805)	0.454 (1.00)
EGFR	37 (34%)	71	0.366 (1.00)	0.497 (1.00)	0.543 (1.00)	0.426 (1.00)	0.537 (1.00)	0.106 (0.795)	0.263 (0.982)	0.974 (1.00)	1 (1.00)	0.0187 (0.604)	0.551 (1.00)	0.125 (0.809)	0.37 (1.00)	0.297 (0.982)	0.00753 (0.604)	0.181 (0.91)	0.0603 (0.677)
KEAP1	12 (11%)	96	0.813 (1.00)	0.256 (0.982)	0.3 (0.982)	0.122 (0.805)	0.582 (1.00)	1 (1.00)	0.883 (1.00)	0.0165 (0.604)	1 (1.00)	0.209 (0.952)	1 (1.00)	0.441 (1.00)	0.0207 (0.604)	0.0279 (0.604)	0.754 (1.00)	0.0277 (0.604)	0.00334 (0.604)
RB1	8 (7%)	100	0.787 (1.00)	0.605 (1.00)	0.338 (1.00)	0.794 (1.00)	0.865 (1.00)	0.416 (1.00)	0.972 (1.00)	0.991 (1.00)	1 (1.00)	0.264 (0.982)		0.629 (1.00)	0.483 (1.00)		0.0714 (0.677)	0.144 (0.829)	1 (1.00)
IL21R	6 (6%)	102	0.667 (1.00)	0.728 (1.00)	0.854 (1.00)	0.12 (0.805)	0.42 (1.00)	0.567 (1.00)	0.758 (1.00)	0.788 (1.00)	1 (1.00)	0.661 (1.00)		1 (1.00)	0.0683 (0.677)	0.265 (0.982)	1 (1.00)	0.416 (1.00)	1 (1.00)
EGFL6	5 (5%)	103	0.509 (1.00)	0.223 (0.954)	0.511 (1.00)	0.781 (1.00)	0.375 (1.00)	0.653 (1.00)	0.16 (0.835)	0.544 (1.00)	1 (1.00)	1 (1.00)		0.569 (1.00)	0.293 (0.982)	0.508 (1.00)	0.389 (1.00)	0.0629 (0.677)	0.647 (1.00)
LMO2	5 (5%)	103	0.732 (1.00)	0.316 (1.00)	0.668 (1.00)	1 (1.00)	0.792 (1.00)	1 (1.00)	0.869 (1.00)	0.634 (1.00)	1 (1.00)	0.167 (0.856)		0.0891 (0.757)	0.703 (1.00)		0.649 (1.00)	0.632 (1.00)	0.14 (0.827)
C10ORF62	4 (4%)	104	0.393 (1.00)	0.672 (1.00)	0.341 (1.00)	0.781 (1.00)	1 (1.00)	0.412 (1.00)	0.837 (1.00)	0.0694 (0.677)	1 (1.00)	1 (1.00)		1 (1.00)	0.36 (1.00)		1 (1.00)	1 (1.00)	0.64 (1.00)
DKK3	4 (4%)	104	0.428 (1.00)	0.67 (1.00)	0.598 (1.00)	0.0947 (0.785)	1 (1.00)	1 (1.00)	0.955 (1.00)	0.776 (1.00)	1 (1.00)	1 (1.00)		1 (1.00)	0.0286 (0.604)	0.0246 (0.604)	0.133 (0.827)	0.796 (1.00)	0.64 (1.00)
BIRC6	6 (6%)	102	0.392 (1.00)	0.935 (1.00)	0.0313 (0.604)	0.0997 (0.795)	1 (1.00)	0.382 (1.00)	0.587 (1.00)	0.973 (1.00)		1 (1.00)		0.569 (1.00)	0.609 (1.00)	0.16 (0.835)	0.698 (1.00)	0.0566 (0.677)	1 (1.00)
TDG	3 (3%)	105	0.617 (1.00)	0.385 (1.00)	0.0791 (0.69)		0.293 (0.982)	0.473 (1.00)	0.202 (0.952)	0.75 (1.00)	1 (1.00)	0.257 (0.982)		1 (1.00)	1 (1.00)		1 (1.00)	0.334 (1.00)	1 (1.00)
C16ORF82	5 (5%)	103	0.555 (1.00)	0.0558 (0.677)	1 (1.00)	0.0318 (0.604)	1 (1.00)	1 (1.00)	0.712 (1.00)	0.227 (0.954)	1 (1.00)	0.663 (1.00)		0.591 (1.00)	0.334 (1.00)	0.186 (0.91)	1 (1.00)	0.682 (1.00)	0.4 (1.00)
GRIK3	9 (8%)	99	0.302 (0.982)	0.488 (1.00)	0.4 (1.00)	0.224 (0.954)	0.268 (0.982)	0.576 (1.00)	0.769 (1.00)	0.147 (0.83)	1 (1.00)	0.715 (1.00)	1 (1.00)	1 (1.00)	0.0463 (0.677)	0.207 (0.952)	0.0746 (0.677)	0.118 (0.805)	0.0318 (0.604)
AFAP1	5 (5%)	103	0.409 (1.00)	0.771 (1.00)	0.209 (0.952)		0.791 (1.00)	0.655 (1.00)	0.617 (1.00)	0.624 (1.00)	1 (1.00)	0.663 (1.00)	0.243 (0.982)	0.569 (1.00)	0.26 (0.982)	0.215 (0.954)	0.0692 (0.677)	0.0356 (0.637)	0.305 (0.982)
CLIP2	7 (6%)	101	0.0375 (0.637)	0.952 (1.00)	0.788 (1.00)	0.353 (1.00)	0.104 (0.795)	0.353 (1.00)	0.516 (1.00)	0.93 (1.00)	1 (1.00)	0.42 (1.00)		0.591 (1.00)	0.294 (0.982)	0.275 (0.982)	1 (1.00)	0.777 (1.00)	0.235 (0.973)
ELFN1	6 (6%)	102	0.538 (1.00)	0.118 (0.805)	0.513 (1.00)	1 (1.00)	1 (1.00)	0.828 (1.00)	0.288 (0.982)	0.783 (1.00)	1 (1.00)	0.661 (1.00)		0.569 (1.00)	0.291 (0.982)		1 (1.00)	0.0755 (0.677)	0.691 (1.00)
TLR7	6 (6%)	102	0.0112 (0.604)	0.884 (1.00)	1 (1.00)	0.352 (1.00)	0.206 (0.952)	0.689 (1.00)	0.863 (1.00)	0.555 (1.00)	1 (1.00)	0.661 (1.00)		1 (1.00)	0.0703 (0.677)	0.83 (1.00)	0.698 (1.00)	0.547 (1.00)	0.691 (1.00)

Methods & Data

Input

Mutation data file = sample_sig_gene_table.txt from Mutsig_2CV pipeline
Processed Mutation data file = /cromwell_root/fc-e7058367-eaa6-44b5-aab5-1ec08acf146a/f466592e-c6e5-4ee3-a314-14eeeca1d630/correlate_genomic_events_all/0d3ab625-b3a9-4a3c-86b8-2befa86be129/call-preprocess_genomic_event/transformed.cor.cli.txt
Clinical data file = /cromwell_root/fc-e7058367-eaa6-44b5-aab5-1ec08acf146a/39eab10a-1791-41cf-866c-13e6472ce02e/normalize_clinical_cptac/df4eac3a-77b6-4ce7-961f-e1027c1ad609/call-normalize_clinical_cptac_task_1/CPTAC3-LUAD-TP.clin.merged.picked.txt
Number of patients = 108
Number of significantly mutated genes = 19
Number of selected clinical features = 17
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)

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