Kidney Renal Papillary Cell Carcinoma: Correlation between gene mutation status and selected clinical features
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/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 14 genes and 8 clinical features across 98 patients, 2 significant findings detected with Q value < 0.25.

- IL32 mutation correlated to 'Time to Death'.

- NFE2L2 mutation correlated to 'AGE'.

Results
Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 14 genes and 8 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 | AGE | GENDER | KARNOFSKY PERFORMANCE SCORE | PATHOLOGY T | PATHOLOGY N | PATHOLOGICSPREAD(M) | TUMOR STAGE
| nMutated (%) | nWild-Type | logrank test | t-test | Fisher's exact test | t-test | Fisher's exact test | Fisher's exact test | Fisher's exact test | Fisher's exact test
IL32 | 4 (4%) | 94 | 1.58e-14 (1.34e-12) | 0.362 (1.00) | 0.304 (1.00) |  | 0.78 (1.00) |  | 0.223 (1.00) | 0.676 (1.00)
NFE2L2 | 3 (3%) | 95 | 0.274 (1.00) | 0.000726 (0.061) | 0.549 (1.00) |  | 0.36 (1.00) |  | 0.407 (1.00) | 0.192 (1.00)
CDC27 | 4 (4%) | 94 | 0.603 (1.00) | 0.778 (1.00) | 0.589 (1.00) |  | 0.78 (1.00) |  | 0.128 (1.00) | 0.354 (1.00)
MET | 7 (7%) | 91 | 0.69 (1.00) | 0.887 (1.00) | 1 (1.00) |  | 1 (1.00) |  | 0.806 (1.00) | 0.894 (1.00)
PCF11 | 7 (7%) | 91 | 0.828 (1.00) | 0.403 (1.00) | 0.426 (1.00) |  | 0.864 (1.00) | 0.204 (1.00) | 0.584 (1.00) | 1 (1.00)
SFRS2IP | 5 (5%) | 93 | 0.233 (1.00) | 0.12 (1.00) | 0.65 (1.00) |  | 0.105 (1.00) | 1 (1.00) | 0.0847 (1.00) | 0.324 (1.00)
LGI4 | 4 (4%) | 94 | 0.189 (1.00) | 0.905 (1.00) | 0.304 (1.00) |  | 0.78 (1.00) |  | 0.703 (1.00) | 0.676 (1.00)
NF2 | 5 (5%) | 93 | 0.603 (1.00) | 0.299 (1.00) | 1 (1.00) |  | 0.404 (1.00) |  | 0.0317 (1.00) | 0.0911 (1.00)
PARD6B | 4 (4%) | 94 | 0.419 (1.00) | 0.74 (1.00) | 0.304 (1.00) |  | 0.173 (1.00) |  | 1 (1.00) | 0.571 (1.00)
BAT2L2 | 4 (4%) | 94 | 0.313 (1.00) | 0.927 (1.00) | 1 (1.00) |  | 0.78 (1.00) |  | 0.624 (1.00) | 0.354 (1.00)
CD86 | 3 (3%) | 95 | 0.743 (1.00) | 0.545 (1.00) | 0.234 (1.00) |  | 1 (1.00) |  |  | 1 (1.00)
POTEH | 3 (3%) | 95 | 0.489 (1.00) | 0.818 (1.00) | 0.549 (1.00) |  | 0.523 (1.00) |  | 0.624 (1.00) | 0.745 (1.00)
SAV1 | 3 (3%) | 95 | 0.69 (1.00) | 0.717 (1.00) | 0.234 (1.00) |  | 0.699 (1.00) |  | 1 (1.00) | 0.354 (1.00)
FLJ46321 | 6 (6%) | 92 | 0.505 (1.00) | 0.318 (1.00) | 1 (1.00) |  | 0.0977 (1.00) |  | 0.338 (1.00) | 0.162 (1.00)

'IL32 MUTATION STATUS' versus 'Time to Death'

P value = 1.58e-14 (logrank test), Q value = 1.3e-12

Table S1. Gene #2: 'IL32 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

| nPatients | nDeath | Duration Range (Median), Month
--- | --- | --- | ---
ALL | 91 | 14 | 0.0 - 182.7 (14.1)
IL32 MUTATED | 4 | 1 | 3.6 - 7.9 (4.8)
IL32 WILD-TYPE | 87 | 13 | 0.0 - 182.7 (15.5)

Figure S1. Get High-res Image Gene #2: 'IL32 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'NFE2L2 MUTATION STATUS' versus 'AGE'

P value = 0.000726 (t-test), Q value = 0.061

Table S2. Gene #9: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

| nPatients | Mean (Std.Dev)
--- | --- | ---
ALL | 95 | 59.6 (12.5)
NFE2L2 MUTATED | 3 | 72.0 (2.6)
NFE2L2 WILD-TYPE | 92 | 59.2 (12.5)

Figure S2. Get High-res Image Gene #9: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

Methods & Data
Input

- Mutation data file = KIRP-TP.mutsig.cluster.txt

- Clinical data file = KIRP-TP.clin.merged.picked.txt

- Number of patients = 98

- Number of significantly mutated genes = 14

- Number of selected clinical features = 8

- 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

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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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] 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)
[4] 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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