This pipeline uses various statistical tests to identify mRNAs whose expression levels correlated to selected clinical features.
Testing the association between 18256 genes and 8 clinical features across 837 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.
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4 genes correlated to 'Time to Death'.
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DIP2B|57609 , PGK1|5230 , CAND1|55832 , IRF2|3660
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677 genes correlated to 'AGE'.
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ESR1|2099 , LRFN5|145581 , TFPI2|7980 , TMEFF1|8577 , SOBP|55084 , ...
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18 genes correlated to 'GENDER'.
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NLGN4Y|22829 , ZFY|7544 , PRKY|5616 , C7ORF10|79783 , SYT9|143425 , ...
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8 genes correlated to 'LYMPH.NODE.METASTASIS'.
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BTBD10|84280 , POLR2B|5431 , SPPL3|121665 , C19ORF21|126353 , SRP72|6731 , ...
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2 genes correlated to 'NUMBER.OF.LYMPH.NODES'.
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HMSD|284293 , FITM2|128486
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No genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION', 'DISTANT.METASTASIS', and 'NEOPLASM.DISEASESTAGE'.
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=4 | shorter survival | N=3 | longer survival | N=1 |
AGE | Spearman correlation test | N=677 | older | N=160 | younger | N=517 |
GENDER | t test | N=18 | male | N=8 | female | N=10 |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=0 | ||||
DISTANT METASTASIS | ANOVA test | N=0 | ||||
LYMPH NODE METASTASIS | ANOVA test | N=8 | ||||
NUMBER OF LYMPH NODES | Spearman correlation test | N=2 | higher number.of.lymph.nodes | N=1 | lower number.of.lymph.nodes | N=1 |
NEOPLASM DISEASESTAGE | ANOVA test | N=0 |
Table S1. Basic characteristics of clinical feature: 'Time to Death'
Time to Death | Duration (Months) | 0-223.4 (median=18.6) |
censored | N = 686 | |
death | N = 94 | |
Significant markers | N = 4 | |
associated with shorter survival | 3 | |
associated with longer survival | 1 |
Table S2. Get Full Table List of 4 genes significantly associated with 'Time to Death' by Cox regression test
HazardRatio | Wald_P | Q | C_index | |
---|---|---|---|---|
DIP2B|57609 | 2.9 | 1.586e-07 | 0.0029 | 0.635 |
PGK1|5230 | 2 | 1.65e-06 | 0.03 | 0.686 |
CAND1|55832 | 2.1 | 1.653e-06 | 0.03 | 0.629 |
IRF2|3660 | 0.28 | 1.982e-06 | 0.036 | 0.329 |
Figure S1. Get High-res Image As an example, this figure shows the association of DIP2B|57609 to 'Time to Death'. four curves present the cumulative survival rates of 4 quartile subsets of patients. P value = 1.59e-07 with univariate Cox regression analysis using continuous log-2 expression values.
![](V1ex.png)
Table S3. Basic characteristics of clinical feature: 'AGE'
AGE | Mean (SD) | 58.2 (13) |
Significant markers | N = 677 | |
pos. correlated | 160 | |
neg. correlated | 517 |
Table S4. Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
ESR1|2099 | 0.3531 | 6.013e-26 | 1.1e-21 |
LRFN5|145581 | -0.2685 | 5.841e-15 | 1.07e-10 |
TFPI2|7980 | -0.2659 | 6.947e-15 | 1.27e-10 |
TMEFF1|8577 | -0.2543 | 8.372e-14 | 1.53e-09 |
SOBP|55084 | -0.252 | 1.415e-13 | 2.58e-09 |
DBX2|440097 | -0.2691 | 2.696e-13 | 4.92e-09 |
DZIP1|22873 | -0.2449 | 6.958e-13 | 1.27e-08 |
PCDH18|54510 | -0.2448 | 7.198e-13 | 1.31e-08 |
RELN|5649 | -0.2466 | 8.742e-13 | 1.6e-08 |
FXYD6|53826 | -0.2408 | 1.723e-12 | 3.14e-08 |
Figure S2. Get High-res Image As an example, this figure shows the association of ESR1|2099 to 'AGE'. P value = 6.01e-26 with Spearman correlation analysis. The straight line presents the best linear regression.
![](V2ex.png)
Table S5. Basic characteristics of clinical feature: 'GENDER'
GENDER | Labels | N |
FEMALE | 828 | |
MALE | 9 | |
Significant markers | N = 18 | |
Higher in MALE | 8 | |
Higher in FEMALE | 10 |
Table S6. Get Full Table List of top 10 genes differentially expressed by 'GENDER'
T(pos if higher in 'MALE') | ttestP | Q | AUC | |
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NLGN4Y|22829 | 41.21 | 2.344e-12 | 4.21e-08 | 1 |
ZFY|7544 | 41.98 | 1.809e-11 | 3.25e-07 | 1 |
PRKY|5616 | 27.63 | 6.148e-10 | 1.1e-05 | 1 |
C7ORF10|79783 | 8.69 | 3.317e-09 | 5.96e-05 | 0.6638 |
SYT9|143425 | 12.45 | 6.607e-09 | 0.000119 | 0.794 |
GSTA1|2938 | -16 | 9.561e-09 | 0.000172 | 0.8833 |
MMP11|4320 | 11.07 | 1.628e-08 | 0.000292 | 0.7465 |
RND2|8153 | 12.29 | 2.69e-08 | 0.000483 | 0.8335 |
SNORA74B|677841 | -11.94 | 9.946e-08 | 0.00179 | 0.8348 |
HTR4|3360 | -12.07 | 1.118e-07 | 0.00201 | 0.7909 |
Figure S3. Get High-res Image As an example, this figure shows the association of NLGN4Y|22829 to 'GENDER'. P value = 2.34e-12 with T-test analysis.
![](V3ex.png)
No gene related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
Table S7. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'
RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N |
NO | 209 | |
YES | 628 | |
Significant markers | N = 0 |
Table S8. Basic characteristics of clinical feature: 'DISTANT.METASTASIS'
DISTANT.METASTASIS | Labels | N |
CM0 (I+) | 2 | |
M0 | 621 | |
M1 | 9 | |
MX | 67 | |
Significant markers | N = 0 |
Table S9. Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'
LYMPH.NODE.METASTASIS | Labels | N |
N0 | 220 | |
N0 (I+) | 13 | |
N0 (I-) | 87 | |
N0 (MOL+) | 1 | |
N1 | 84 | |
N1A | 109 | |
N1B | 26 | |
N1C | 2 | |
N1MI | 20 | |
N2 | 42 | |
N2A | 45 | |
N3 | 12 | |
N3A | 27 | |
N3B | 1 | |
NX | 10 | |
Significant markers | N = 8 |
Table S10. Get Full Table List of 8 genes differentially expressed by 'LYMPH.NODE.METASTASIS'
ANOVA_P | Q | |
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BTBD10|84280 | 8.892e-14 | 1.62e-09 |
POLR2B|5431 | 4.148e-09 | 7.57e-05 |
SPPL3|121665 | 2.033e-07 | 0.00371 |
C19ORF21|126353 | 5.823e-07 | 0.0106 |
SRP72|6731 | 6.716e-07 | 0.0123 |
ZNF837|116412 | 7.758e-07 | 0.0142 |
FAM128B|80097 | 1.419e-06 | 0.0259 |
PXT1|222659 | 2.166e-06 | 0.0395 |
Figure S4. Get High-res Image As an example, this figure shows the association of BTBD10|84280 to 'LYMPH.NODE.METASTASIS'. P value = 8.89e-14 with ANOVA analysis.
![](V6ex.png)
Table S11. Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'
NUMBER.OF.LYMPH.NODES | Mean (SD) | 2.16 (4.3) |
Significant markers | N = 2 | |
pos. correlated | 1 | |
neg. correlated | 1 |
Table S12. Get Full Table List of 2 genes significantly correlated to 'NUMBER.OF.LYMPH.NODES' by Spearman correlation test
SpearmanCorr | corrP | Q | |
---|---|---|---|
HMSD|284293 | -0.2591 | 9.257e-08 | 0.00169 |
FITM2|128486 | 0.1796 | 1.867e-06 | 0.0341 |
Figure S5. Get High-res Image As an example, this figure shows the association of HMSD|284293 to 'NUMBER.OF.LYMPH.NODES'. P value = 9.26e-08 with Spearman correlation analysis. The straight line presents the best linear regression.
![](V7ex.png)
Table S13. Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'
NEOPLASM.DISEASESTAGE | Labels | N |
STAGE I | 68 | |
STAGE IA | 44 | |
STAGE IB | 3 | |
STAGE II | 8 | |
STAGE IIA | 240 | |
STAGE IIB | 160 | |
STAGE III | 2 | |
STAGE IIIA | 100 | |
STAGE IIIB | 20 | |
STAGE IIIC | 32 | |
STAGE IV | 9 | |
STAGE X | 12 | |
Significant markers | N = 0 |
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Expresson data file = BRCA-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
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Clinical data file = BRCA-TP.clin.merged.picked.txt
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Number of patients = 837
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Number of genes = 18256
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Number of clinical features = 8
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 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 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 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.