This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.
Testing the association between 17419 genes and 8 clinical features across 299 samples, statistically thresholded by Q value < 0.05, 6 clinical features related to at least one genes.
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2 genes correlated to 'Time to Death'.
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ZNF266 , WIPI1
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4 genes correlated to 'AGE'.
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SLC35D3 , HAND1 , XKR6 , PRSS27
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5 genes correlated to 'GENDER'.
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KIF4B , FRG1B , SLC22A3 , NLRP2 , RPA1
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7 genes correlated to 'PATHOLOGY.N'.
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SLC47A2 , AVPI1 , FAM185A , ARHGAP27 , ESRRA , ...
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7 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
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FLII , ZCCHC17 , RTN4IP1 , CKS2 , RPL7L1 , ...
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3 genes correlated to 'NEOADJUVANT.THERAPY'.
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ASRGL1 , ZCCHC17 , BMP6
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No genes correlated to 'PATHOLOGY.T', and 'TUMOR.STAGE'.
Complete statistical result table is provided in Supplement Table 1
Clinical feature | Statistical test | Significant genes | Associated with | Associated with | ||
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Time to Death | Cox regression test | N=2 | shorter survival | N=1 | longer survival | N=1 |
AGE | Spearman correlation test | N=4 | older | N=4 | younger | N=0 |
GENDER | t test | N=5 | male | N=2 | female | N=3 |
PATHOLOGY T | Spearman correlation test | N=0 | ||||
PATHOLOGY N | Spearman correlation test | N=7 | higher pN | N=7 | lower pN | N=0 |
TUMOR STAGE | Spearman correlation test | N=0 | ||||
RADIATIONS RADIATION REGIMENINDICATION | t test | N=7 | yes | N=1 | no | N=6 |
NEOADJUVANT THERAPY | t test | N=3 | yes | N=2 | no | N=1 |
Time to Death | Duration (Months) | 0.1-210.9 (median=14.8) |
censored | N = 179 | |
death | N = 117 | |
Significant markers | N = 2 | |
associated with shorter survival | 1 | |
associated with longer survival | 1 |
AGE | Mean (SD) | 61.14 (12) |
Significant markers | N = 4 | |
pos. correlated | 4 | |
neg. correlated | 0 |
SpearmanCorr | corrP | Q | |
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SLC35D3 | 0.3072 | 5.932e-08 | 0.00103 |
HAND1 | 0.2824 | 6.878e-07 | 0.012 |
XKR6 | 0.2808 | 8.002e-07 | 0.0139 |
PRSS27 | 0.2672 | 2.774e-06 | 0.0483 |
GENDER | Labels | N |
FEMALE | 81 | |
MALE | 218 | |
Significant markers | N = 5 | |
Higher in MALE | 2 | |
Higher in FEMALE | 3 |
T(pos if higher in 'MALE') | ttestP | Q | AUC | |
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KIF4B | -11.42 | 1.288e-21 | 2.24e-17 | 0.8553 |
FRG1B | -5.97 | 2.708e-08 | 0.000472 | 0.7198 |
SLC22A3 | 5.3 | 2.257e-07 | 0.00393 | 0.5962 |
NLRP2 | 5.07 | 1.269e-06 | 0.0221 | 0.6906 |
RPA1 | -4.91 | 1.524e-06 | 0.0265 | 0.5609 |
PATHOLOGY.T | Mean (SD) | 2.92 (1) |
N | ||
T1 | 23 | |
T2 | 77 | |
T3 | 59 | |
T4 | 101 | |
Significant markers | N = 0 |
PATHOLOGY.N | Mean (SD) | 1.03 (0.96) |
N | ||
N0 | 99 | |
N1 | 32 | |
N2 | 96 | |
N3 | 5 | |
Significant markers | N = 7 | |
pos. correlated | 7 | |
neg. correlated | 0 |
SpearmanCorr | corrP | Q | |
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SLC47A2 | 0.356 | 2.457e-08 | 0.000428 |
AVPI1 | 0.3295 | 2.805e-07 | 0.00489 |
FAM185A | 0.3168 | 8.333e-07 | 0.0145 |
ARHGAP27 | 0.3158 | 9.112e-07 | 0.0159 |
ESRRA | 0.3039 | 2.415e-06 | 0.0421 |
VAMP8 | 0.3031 | 2.559e-06 | 0.0446 |
BTNL8 | 0.3018 | 2.853e-06 | 0.0497 |
TUMOR.STAGE | Mean (SD) | 3.29 (0.98) |
N | ||
Stage 1 | 16 | |
Stage 2 | 47 | |
Stage 3 | 40 | |
Stage 4 | 152 | |
Significant markers | N = 0 |
7 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N |
NO | 75 | |
YES | 224 | |
Significant markers | N = 7 | |
Higher in YES | 1 | |
Higher in NO | 6 |
T(pos if higher in 'YES') | ttestP | Q | AUC | |
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FLII | 5.7 | 4.461e-08 | 0.000777 | 0.693 |
ZCCHC17 | -5.65 | 1.054e-07 | 0.00184 | 0.7057 |
RTN4IP1 | -5.29 | 4.899e-07 | 0.00853 | 0.6849 |
CKS2 | -5.17 | 8.851e-07 | 0.0154 | 0.6911 |
RPL7L1 | -5.08 | 1.176e-06 | 0.0205 | 0.6839 |
EHMT2 | -5.02 | 1.234e-06 | 0.0215 | 0.6693 |
TMEM57 | -5.01 | 1.786e-06 | 0.0311 | 0.6988 |
NEOADJUVANT.THERAPY | Labels | N |
NO | 45 | |
YES | 254 | |
Significant markers | N = 3 | |
Higher in YES | 2 | |
Higher in NO | 1 |
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Expresson data file = HNSC.meth.for_correlation.filtered_data.txt
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Clinical data file = HNSC.clin.merged.picked.txt
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Number of patients = 299
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Number of genes = 17419
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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 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.