This pipeline uses various statistical tests to identify mRNAs whose expression levels correlated to selected clinical features.
Testing the association between 17814 genes and 19 clinical features across 1593 samples, statistically thresholded by Q value < 0.05, 16 clinical features related to at least one genes.
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3018 genes correlated to 'Time to Death'.
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KLHL14 , ASS1 , IGSF11 , UPK1B , C4ORF32 , ...
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3682 genes correlated to 'AGE'.
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GREB1 , COL18A1 , DUOX2 , LDOC1 , GALNTL1 , ...
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17315 genes correlated to 'PRIMARY.SITE.OF.DISEASE'.
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KLHL14 , ZG16 , SLC22A2 , PDZD3 , EMX2 , ...
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8993 genes correlated to 'GENDER'.
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ESR1 , RSPO1 , DDX3Y , RPS4Y1 , EIF1AY , ...
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206 genes correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.
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PPP1R9A , VASN , MARCH7 , CCDC135 , POGZ , ...
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16971 genes correlated to 'HISTOLOGICAL.TYPE'.
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KLHL14 , PDZD3 , EMX2 , NPR1 , FUT4 , ...
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5911 genes correlated to 'PATHOLOGY.T'.
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C13ORF3 , NR3C1 , CDCA7 , LIFR , C20ORF151 , ...
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16 genes correlated to 'PATHOLOGY.N'.
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TNFRSF10C , FAM73A , MGC50559 , ZNF273 , GABARAP , ...
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30 genes correlated to 'PATHOLOGICSPREAD(M)'.
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KCNC2 , TCF7 , HCN1 , C8ORF30A , SPACA3 , ...
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7395 genes correlated to 'TUMOR.STAGE'.
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FGF18 , WT1 , KITLG , RBM38 , ELL2 , ...
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5814 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
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CYP3A5 , CYP3A7 , CYP3A4 , TCF21 , MAP2K7 , ...
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9 genes correlated to 'TOBACCOSMOKINGHISTORYINDICATOR'.
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PSME4 , C1ORF64 , LMNB2 , LONP1 , SLC25A1 , ...
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1 gene correlated to 'YEAROFTOBACCOSMOKINGONSET'.
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MMP10
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2 genes correlated to 'LYMPH.NODE.METASTASIS'.
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GUCA2A , ASZ1
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2319 genes correlated to 'COMPLETENESS.OF.RESECTION'.
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NPR1 , WIT1 , DOK5 , THRSP , KLHL14 , ...
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5 genes correlated to 'NEOPLASM.DISEASESTAGE'.
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PGC , BMPER , LRP4 , GPER , PRSS2
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No genes correlated to 'NUMBERPACKYEARSSMOKED', 'DISTANT.METASTASIS', and 'NUMBER.OF.LYMPH.NODES'.
Complete statistical result table is provided in Supplement Table 1
Clinical feature | Statistical test | Significant genes | Associated with | Associated with | ||
---|---|---|---|---|---|---|
Time to Death | Cox regression test | N=3018 | shorter survival | N=1360 | longer survival | N=1658 |
AGE | Spearman correlation test | N=3682 | older | N=1748 | younger | N=1934 |
PRIMARY SITE OF DISEASE | ANOVA test | N=17315 | ||||
GENDER | t test | N=8993 | male | N=4112 | female | N=4881 |
KARNOFSKY PERFORMANCE SCORE | Spearman correlation test | N=206 | higher score | N=129 | lower score | N=77 |
HISTOLOGICAL TYPE | ANOVA test | N=16971 | ||||
PATHOLOGY T | Spearman correlation test | N=5911 | higher pT | N=3176 | lower pT | N=2735 |
PATHOLOGY N | Spearman correlation test | N=16 | higher pN | N=3 | lower pN | N=13 |
PATHOLOGICSPREAD(M) | ANOVA test | N=30 | ||||
TUMOR STAGE | Spearman correlation test | N=7395 | higher stage | N=3996 | lower stage | N=3399 |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=5814 | yes | N=2865 | no | N=2949 |
NUMBERPACKYEARSSMOKED | Spearman correlation test | N=0 | ||||
TOBACCOSMOKINGHISTORYINDICATOR | ANOVA test | N=9 | ||||
YEAROFTOBACCOSMOKINGONSET | Spearman correlation test | N=1 | higher yearoftobaccosmokingonset | N=0 | lower yearoftobaccosmokingonset | N=1 |
DISTANT METASTASIS | ANOVA test | N=0 | ||||
LYMPH NODE METASTASIS | ANOVA test | N=2 | ||||
COMPLETENESS OF RESECTION | ANOVA test | N=2319 | ||||
NUMBER OF LYMPH NODES | Spearman correlation test | N=0 | ||||
NEOPLASM DISEASESTAGE | ANOVA test | N=5 |
Time to Death | Duration (Months) | 0.1-223.4 (median=23) |
censored | N = 1000 | |
death | N = 437 | |
Significant markers | N = 3018 | |
associated with shorter survival | 1360 | |
associated with longer survival | 1658 |
HazardRatio | Wald_P | Q | C_index | |
---|---|---|---|---|
KLHL14 | 1.26 | 0 | 0 | 0.6 |
ASS1 | 1.32 | 0 | 0 | 0.621 |
IGSF11 | 1.36 | 0 | 0 | 0.641 |
UPK1B | 1.21 | 0 | 0 | 0.636 |
C4ORF32 | 0.77 | 0 | 0 | 0.38 |
ZRSR1 | 0.55 | 0 | 0 | 0.349 |
MDS1 | 1.37 | 0 | 0 | 0.621 |
GALNT12 | 1.31 | 0 | 0 | 0.616 |
MUC4 | 1.22 | 0 | 0 | 0.635 |
NUBP1 | 0.46 | 0 | 0 | 0.354 |
AGE | Mean (SD) | 61.39 (13) |
Significant markers | N = 3682 | |
pos. correlated | 1748 | |
neg. correlated | 1934 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
GREB1 | -0.288 | 1.648e-31 | 2.94e-27 |
COL18A1 | -0.2771 | 3.469e-29 | 6.18e-25 |
DUOX2 | 0.2769 | 3.755e-29 | 6.69e-25 |
LDOC1 | -0.2689 | 1.588e-27 | 2.83e-23 |
GALNTL1 | -0.2672 | 3.515e-27 | 6.26e-23 |
OBSL1 | -0.2646 | 1.107e-26 | 1.97e-22 |
FOXF1 | 0.262 | 3.685e-26 | 6.56e-22 |
CYP2C18 | 0.2605 | 6.935e-26 | 1.23e-21 |
BBOX1 | -0.2573 | 2.842e-25 | 5.06e-21 |
SH3BP5 | -0.2572 | 3.097e-25 | 5.51e-21 |
PRIMARY.SITE.OF.DISEASE | Labels | N |
BREAST | 526 | |
COLON | 152 | |
ENDOMETRIAL | 54 | |
KIDNEY | 72 | |
LUNG | 186 | |
OMENTUM | 2 | |
OVARY | 529 | |
PERITONEUM (OVARY) | 2 | |
RECTUM | 68 | |
Significant markers | N = 17315 |
ANOVA_P | Q | |
---|---|---|
KLHL14 | 0 | 0 |
ZG16 | 0 | 0 |
SLC22A2 | 0 | 0 |
PDZD3 | 0 | 0 |
EMX2 | 0 | 0 |
NPR1 | 0 | 0 |
FUT4 | 0 | 0 |
ACF | 0 | 0 |
FXYD2 | 0 | 0 |
UPK1B | 0 | 0 |
GENDER | Labels | N |
FEMALE | 1304 | |
MALE | 289 | |
Significant markers | N = 8993 | |
Higher in MALE | 4112 | |
Higher in FEMALE | 4881 |
T(pos if higher in 'MALE') | ttestP | Q | AUC | |
---|---|---|---|---|
ESR1 | -36.23 | 6.789e-167 | 1.21e-162 | 0.8781 |
RSPO1 | -31.56 | 9.619e-167 | 1.71e-162 | 0.8493 |
DDX3Y | 53.31 | 9.336e-164 | 1.66e-159 | 0.9839 |
RPS4Y1 | 51.76 | 1.437e-155 | 2.56e-151 | 0.9717 |
EIF1AY | 48.93 | 2.175e-151 | 3.87e-147 | 0.9839 |
RPS4Y2 | 48.54 | 8.57e-148 | 1.53e-143 | 0.9816 |
ERBB4 | -32.63 | 1.134e-147 | 2.02e-143 | 0.8588 |
JARID1D | 44.53 | 5.72e-147 | 1.02e-142 | 0.9762 |
SCGB2A2 | -29.47 | 7.483e-146 | 1.33e-141 | 0.8574 |
CYORF15A | 43.55 | 3.378e-139 | 6.01e-135 | 0.9813 |
206 genes related to 'KARNOFSKY.PERFORMANCE.SCORE'.
KARNOFSKY.PERFORMANCE.SCORE | Mean (SD) | 60.22 (34) |
Significant markers | N = 206 | |
pos. correlated | 129 | |
neg. correlated | 77 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
PPP1R9A | 0.5916 | 4.259e-10 | 7.59e-06 |
VASN | 0.5749 | 1.671e-09 | 2.98e-05 |
MARCH7 | -0.5551 | 7.711e-09 | 0.000137 |
CCDC135 | 0.5548 | 7.875e-09 | 0.00014 |
POGZ | 0.5503 | 1.102e-08 | 0.000196 |
INSIG2 | -0.5485 | 1.255e-08 | 0.000223 |
ZNF503 | 0.5479 | 1.318e-08 | 0.000235 |
TLE1 | 0.5448 | 1.642e-08 | 0.000292 |
ADK | -0.5439 | 1.761e-08 | 0.000314 |
PCYT1A | -0.5421 | 1.996e-08 | 0.000355 |
HISTOLOGICAL.TYPE | Labels | N |
COLON ADENOCARCINOMA | 126 | |
COLON MUCINOUS ADENOCARCINOMA | 24 | |
ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA | 41 | |
INFILTRATING DUCTAL CARCINOMA | 110 | |
INFILTRATING LOBULAR CARCINOMA | 12 | |
KIDNEY CLEAR CELL RENAL CARCINOMA | 72 | |
LUNG ADENOCARCINOMA MIXED SUBTYPE | 1 | |
LUNG ADENOCARCINOMA- NOT OTHERWISE SPECIFIED (NOS) | 30 | |
LUNG BASALOID SQUAMOUS CELL CARCINOMA | 5 | |
LUNG CLEAR CELL ADENOCARCINOMA | 1 | |
LUNG PAPILLARY SQUAMOUS CELL CARICNOMA | 1 | |
LUNG SQUAMOUS CELL CARCINOMA- NOT OTHERWISE SPECIFIED (NOS) | 148 | |
MIXED HISTOLOGY (PLEASE SPECIFY) | 5 | |
MIXED SEROUS AND ENDOMETRIOID | 1 | |
OTHER SPECIFY | 10 | |
RECTAL ADENOCARCINOMA | 58 | |
RECTAL MUCINOUS ADENOCARCINOMA | 7 | |
SEROUS CYSTADENOCARCINOMA | 533 | |
SEROUS ENDOMETRIAL ADENOCARCINOMA | 12 | |
Significant markers | N = 16971 |
ANOVA_P | Q | |
---|---|---|
KLHL14 | 0 | 0 |
PDZD3 | 0 | 0 |
EMX2 | 0 | 0 |
NPR1 | 0 | 0 |
FUT4 | 0 | 0 |
ACF | 0 | 0 |
FXYD2 | 0 | 0 |
SPINK4 | 0 | 0 |
SFTPC | 0 | 0 |
SLC12A2 | 0 | 0 |
PATHOLOGY.T | Mean (SD) | 2.3 (0.85) |
N | ||
T1 | 92 | |
T2 | 179 | |
T3 | 178 | |
T4 | 29 | |
Significant markers | N = 5911 | |
pos. correlated | 3176 | |
neg. correlated | 2735 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
C13ORF3 | 0.5211 | 1.264e-34 | 2.25e-30 |
NR3C1 | -0.5184 | 3.085e-34 | 5.49e-30 |
CDCA7 | 0.5156 | 7.924e-34 | 1.41e-29 |
LIFR | -0.5143 | 1.235e-33 | 2.2e-29 |
C20ORF151 | 0.5111 | 3.619e-33 | 6.45e-29 |
NOXO1 | 0.5077 | 1.096e-32 | 1.95e-28 |
PDSS1 | 0.5062 | 1.784e-32 | 3.18e-28 |
B3GNT3 | 0.5004 | 1.188e-31 | 2.12e-27 |
MAL | -0.4987 | 2.023e-31 | 3.6e-27 |
POF1B | 0.4978 | 2.687e-31 | 4.78e-27 |
PATHOLOGY.N | Mean (SD) | 0.51 (0.77) |
N | ||
N0 | 290 | |
N1 | 90 | |
N2 | 60 | |
N3 | 5 | |
Significant markers | N = 16 | |
pos. correlated | 3 | |
neg. correlated | 13 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
TNFRSF10C | -0.2603 | 2.519e-08 | 0.000449 |
FAM73A | -0.2572 | 3.746e-08 | 0.000667 |
MGC50559 | -0.2477 | 1.198e-07 | 0.00213 |
ZNF273 | 0.2452 | 1.624e-07 | 0.00289 |
GABARAP | -0.2423 | 2.285e-07 | 0.00407 |
LUZP2 | 0.2388 | 3.561e-07 | 0.00634 |
CNDP2 | -0.2304 | 8.931e-07 | 0.0159 |
DHCR7 | 0.2301 | 9.331e-07 | 0.0166 |
ZFP2 | -0.2294 | 1.007e-06 | 0.0179 |
DCTN6 | -0.2263 | 1.417e-06 | 0.0252 |
PATHOLOGICSPREAD(M) | Labels | N |
M0 | 428 | |
M1 | 44 | |
M1A | 1 | |
Significant markers | N = 30 |
ANOVA_P | Q | |
---|---|---|
KCNC2 | 1.224e-09 | 2.18e-05 |
TCF7 | 2.424e-08 | 0.000432 |
HCN1 | 5.782e-08 | 0.00103 |
C8ORF30A | 1.136e-07 | 0.00202 |
SPACA3 | 2.624e-07 | 0.00467 |
F10 | 4.444e-07 | 0.00791 |
RBM26 | 5.393e-07 | 0.0096 |
SERPINA4 | 6.055e-07 | 0.0108 |
NPAS2 | 7.627e-07 | 0.0136 |
PLOD3 | 9.144e-07 | 0.0163 |
TUMOR.STAGE | Mean (SD) | 2.55 (0.95) |
N | ||
Stage 1 | 206 | |
Stage 2 | 163 | |
Stage 3 | 512 | |
Stage 4 | 120 | |
Significant markers | N = 7395 | |
pos. correlated | 3996 | |
neg. correlated | 3399 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
FGF18 | 0.5209 | 1.067e-70 | 1.9e-66 |
WT1 | 0.5115 | 7.953e-68 | 1.42e-63 |
KITLG | -0.4949 | 5.798e-63 | 1.03e-58 |
RBM38 | 0.4891 | 2.517e-61 | 4.48e-57 |
ELL2 | -0.4855 | 2.59e-60 | 4.61e-56 |
RIMS4 | 0.4826 | 1.629e-59 | 2.9e-55 |
DOK7 | 0.4818 | 2.551e-59 | 4.54e-55 |
ZNF503 | 0.4817 | 2.85e-59 | 5.07e-55 |
KLK8 | 0.4805 | 5.754e-59 | 1.02e-54 |
KLK6 | 0.4795 | 1.078e-58 | 1.92e-54 |
5814 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N |
NO | 180 | |
YES | 1413 | |
Significant markers | N = 5814 | |
Higher in YES | 2865 | |
Higher in NO | 2949 |
T(pos if higher in 'YES') | ttestP | Q | AUC | |
---|---|---|---|---|
CYP3A5 | 22.2 | 4.3e-77 | 7.66e-73 | 0.7877 |
CYP3A7 | 20.4 | 1.717e-68 | 3.06e-64 | 0.7635 |
CYP3A4 | 20.24 | 6.476e-68 | 1.15e-63 | 0.7729 |
TCF21 | 21.02 | 1.431e-65 | 2.55e-61 | 0.7939 |
MAP2K7 | 21.32 | 8.132e-65 | 1.45e-60 | 0.8098 |
AADAC | 20.04 | 4.24e-63 | 7.55e-59 | 0.7714 |
CCDC71 | 21.22 | 1.383e-62 | 2.46e-58 | 0.8195 |
REG1A | 19.08 | 5.442e-59 | 9.69e-55 | 0.773 |
CHMP4B | 20.11 | 6.206e-58 | 1.11e-53 | 0.8105 |
PDZD3 | 17.13 | 1.326e-57 | 2.36e-53 | 0.6836 |
NUMBERPACKYEARSSMOKED | Mean (SD) | 53.05 (35) |
Significant markers | N = 0 |
9 genes related to 'TOBACCOSMOKINGHISTORYINDICATOR'.
TOBACCOSMOKINGHISTORYINDICATOR | Labels | N |
CURRENT REFORMED SMOKER FOR < OR = 15 YEARS | 93 | |
CURRENT REFORMED SMOKER FOR > 15 YEARS | 49 | |
CURRENT SMOKER | 31 | |
LIFELONG NON-SMOKER | 11 | |
Significant markers | N = 9 |
ANOVA_P | Q | |
---|---|---|
PSME4 | 6.816e-08 | 0.00121 |
C1ORF64 | 1.645e-07 | 0.00293 |
LMNB2 | 1.211e-06 | 0.0216 |
LONP1 | 1.573e-06 | 0.028 |
SLC25A1 | 1.62e-06 | 0.0289 |
IGFBP7 | 1.965e-06 | 0.035 |
N6AMT2 | 2.361e-06 | 0.0421 |
CATSPER3 | 2.469e-06 | 0.044 |
LAS1L | 2.63e-06 | 0.0468 |
YEAROFTOBACCOSMOKINGONSET | Mean (SD) | 1959.74 (11) |
Significant markers | N = 1 | |
pos. correlated | 0 | |
neg. correlated | 1 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
MMP10 | -0.4473 | 4.812e-07 | 0.00857 |
DISTANT.METASTASIS | Labels | N |
CM0 (I+) | 2 | |
M0 | 369 | |
M1 | 8 | |
MX | 10 | |
Significant markers | N = 0 |
LYMPH.NODE.METASTASIS | Labels | N |
N0 | 118 | |
N0 (I+) | 7 | |
N0 (I-) | 59 | |
N1 | 41 | |
N1A | 62 | |
N1B | 14 | |
N1C | 2 | |
N1MI | 11 | |
N2 | 24 | |
N2A | 24 | |
N3 | 5 | |
N3A | 16 | |
NX | 6 | |
Significant markers | N = 2 |
2319 genes related to 'COMPLETENESS.OF.RESECTION'.
COMPLETENESS.OF.RESECTION | Labels | N |
R0 | 403 | |
R1 | 39 | |
R2 | 34 | |
RX | 7 | |
Significant markers | N = 2319 |
ANOVA_P | Q | |
---|---|---|
NPR1 | 2.596e-40 | 4.62e-36 |
WIT1 | 2.503e-37 | 4.46e-33 |
DOK5 | 4.72e-35 | 8.41e-31 |
THRSP | 5.822e-35 | 1.04e-30 |
KLHL14 | 3.091e-34 | 5.51e-30 |
WT1 | 1.009e-33 | 1.8e-29 |
S100A1 | 2.162e-33 | 3.85e-29 |
LYPD1 | 3.811e-30 | 6.79e-26 |
MUC16 | 8.048e-29 | 1.43e-24 |
SCGB1D2 | 1.049e-28 | 1.87e-24 |
NUMBER.OF.LYMPH.NODES | Mean (SD) | 1.94 (4) |
Significant markers | N = 0 |
NEOPLASM.DISEASESTAGE | Labels | N |
STAGE I | 41 | |
STAGE IA | 22 | |
STAGE IB | 2 | |
STAGE IIA | 136 | |
STAGE IIB | 83 | |
STAGE IIIA | 60 | |
STAGE IIIB | 12 | |
STAGE IIIC | 14 | |
STAGE IV | 8 | |
STAGE X | 11 | |
Significant markers | N = 5 |
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Expresson data file = PANCAN12-TP.medianexp.txt
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Clinical data file = PANCAN12-TP.clin.merged.picked.txt
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Number of patients = 1593
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Number of genes = 17814
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Number of clinical features = 19
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.