This pipeline uses various statistical tests to identify RPPAs whose expression levels correlated to selected clinical features.
Testing the association between 165 genes and 6 clinical features across 407 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.
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2 genes correlated to 'Time to Death'.
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MAPK1 MAPK3|MAPK_PT202_Y204-R-V , MAP2K1|MEK1_PS217_S221-R-V
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4 genes correlated to 'AGE'.
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PGR|PR-R-V , ERBB2|HER2-M-V , ESR1|ER-ALPHA-R-V , ERBB2|HER2_PY1248-R-V
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3 genes correlated to 'TUMOR.STAGE'.
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PEA15|PEA-15-R-V , RAF1|C-RAF_PS338-R-C , CDKN1B|P27_PT157-R-C
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No genes correlated to 'PRIMARY.SITE.OF.DISEASE', 'KARNOFSKY.PERFORMANCE.SCORE', and 'COMPLETENESS.OF.RESECTION'.
Complete statistical result table is provided in Supplement Table 1
Table 1. Get Full Table This table shows the clinical features, statistical methods used, and the number of genes that are significantly associated with each clinical feature at Q value < 0.05.
| Clinical feature | Statistical test | Significant genes | Associated with | Associated with | ||
|---|---|---|---|---|---|---|
| Time to Death | Cox regression test | N=2 | shorter survival | N=2 | longer survival | N=0 |
| AGE | Spearman correlation test | N=4 | older | N=3 | younger | N=1 |
| PRIMARY SITE OF DISEASE | ANOVA test | N=0 | ||||
| KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=0 | ||||
| TUMOR STAGE | Spearman correlation test | N=3 | higher stage | N=1 | lower stage | N=2 |
| COMPLETENESS OF RESECTION | t test | N=0 |
Table S1. Basic characteristics of clinical feature: 'Time to Death'
| Time to Death | Duration (Months) | 0.3-180.2 (median=28.6) |
| censored | N = 191 | |
| death | N = 209 | |
| Significant markers | N = 2 | |
| associated with shorter survival | 2 | |
| associated with longer survival | 0 |
Table S2. Get Full Table List of 2 genes significantly associated with 'Time to Death' by Cox regression test
| HazardRatio | Wald_P | Q | C_index | |
|---|---|---|---|---|
| MAPK1 MAPK3|MAPK_PT202_Y204-R-V | 1.27 | 0.0001888 | 0.031 | 0.572 |
| MAP2K1|MEK1_PS217_S221-R-V | 1.87 | 0.0002402 | 0.039 | 0.577 |
Figure S1. Get High-res Image As an example, this figure shows the association of MAPK1 MAPK3|MAPK_PT202_Y204-R-V to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 0.000189 with univariate Cox regression analysis using continuous log-2 expression values.
Table S3. Basic characteristics of clinical feature: 'AGE'
| AGE | Mean (SD) | 59.69 (12) |
| Significant markers | N = 4 | |
| pos. correlated | 3 | |
| neg. correlated | 1 |
Table S4. Get Full Table List of 4 genes significantly correlated to 'AGE' by Spearman correlation test
| SpearmanCorr | corrP | Q | |
|---|---|---|---|
| PGR|PR-R-V | -0.1942 | 9.269e-05 | 0.0153 |
| ERBB2|HER2-M-V | 0.1886 | 0.0001484 | 0.0243 |
| ESR1|ER-ALPHA-R-V | 0.1882 | 0.0001536 | 0.025 |
| ERBB2|HER2_PY1248-R-V | 0.1843 | 0.0002109 | 0.0342 |
Figure S2. Get High-res Image As an example, this figure shows the association of PGR|PR-R-V to 'AGE'. P value = 9.27e-05 with Spearman correlation analysis. The straight line presents the best linear regression.
Table S5. Basic characteristics of clinical feature: 'PRIMARY.SITE.OF.DISEASE'
| PRIMARY.SITE.OF.DISEASE | Labels | N |
| OMENTUM | 2 | |
| OVARY | 403 | |
| PERITONEUM (OVARY) | 2 | |
| Significant markers | N = 0 |
No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.
Table S6. Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'
| KARNOFSKY.PERFORMANCE.SCORE | Mean (SD) | 74.9 (12) |
| Score | N | |
| 40 | 1 | |
| 60 | 14 | |
| 80 | 33 | |
| 100 | 3 | |
| Significant markers | N = 0 |
Table S7. Basic characteristics of clinical feature: 'TUMOR.STAGE'
| TUMOR.STAGE | Mean (SD) | 3.01 (0.56) |
| N | ||
| Stage 1 | 14 | |
| Stage 2 | 19 | |
| Stage 3 | 317 | |
| Stage 4 | 52 | |
| Significant markers | N = 3 | |
| pos. correlated | 1 | |
| neg. correlated | 2 |
Table S8. Get Full Table List of 3 genes significantly correlated to 'TUMOR.STAGE' by Spearman correlation test
| SpearmanCorr | corrP | Q | |
|---|---|---|---|
| PEA15|PEA-15-R-V | 0.232 | 2.578e-06 | 0.000425 |
| RAF1|C-RAF_PS338-R-C | -0.1836 | 0.000214 | 0.0351 |
| CDKN1B|P27_PT157-R-C | -0.1806 | 0.0002723 | 0.0444 |
Figure S3. Get High-res Image As an example, this figure shows the association of PEA15|PEA-15-R-V to 'TUMOR.STAGE'. P value = 2.58e-06 with Spearman correlation analysis.
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Expresson data file = OV-TP.rppa.txt
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Clinical data file = OV-TP.clin.merged.picked.txt
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Number of patients = 407
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Number of genes = 165
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Number of clinical features = 6
For survival clinical features, Wald's test in univariate Cox regression analysis with proportional hazards model (Andersen and Gill 1982) was used to estimate the P values using the 'coxph' function in R. Kaplan-Meier survival curves were plot using the four quartile subgroups of patients based on expression levels
For continuous numerical clinical features, Spearman's rank correlation coefficients (Spearman 1904) and two-tailed P values were estimated using 'cor.test' function in R
For multi-class clinical features (ordinal or nominal), one-way analysis of variance (Howell 2002) was applied to compare the log2-expression levels between different clinical classes using 'anova' function in R
For two-class clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the log2-expression levels between the two clinical classes using 't.test' function in R
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.
This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.