This pipeline uses various statistical tests to identify genes whose promoter methylation levels correlated to selected clinical features.
Testing the association between 17460 genes and 8 clinical features across 283 samples, statistically thresholded by Q value < 0.05, 7 clinical features related to at least one genes.
-
2 genes correlated to 'Time to Death'.
-
ZNF266 , HES7
-
4 genes correlated to 'AGE'.
-
SLC35D3 , XKR6 , DES , HAND1
-
8 genes correlated to 'GENDER'.
-
KIF4B , LOC96610 , FH , FRG1B , SLC22A3 , ...
-
5 genes correlated to 'PATHOLOGY.N'.
-
SLC47A2 , ESRRA , AVPI1 , FGD2 , TMCO4
-
1 gene correlated to 'TUMOR.STAGE'.
-
LOC400657
-
2 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
-
ZCCHC17 , NEAT1
-
4 genes correlated to 'NEOADJUVANT.THERAPY'.
-
ASRGL1 , ZCCHC17 , NEAT1 , BMP6
-
No genes correlated to 'PATHOLOGY.T'
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=2 | shorter survival | N=2 | longer survival | N=0 |
AGE | Spearman correlation test | N=4 | older | N=4 | younger | N=0 |
GENDER | t test | N=8 | male | N=5 | female | N=3 |
PATHOLOGY T | Spearman correlation test | N=0 | ||||
PATHOLOGY N | Spearman correlation test | N=5 | higher pN | N=5 | lower pN | N=0 |
TUMOR STAGE | Spearman correlation test | N=1 | higher stage | N=1 | lower stage | N=0 |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=2 | yes | N=1 | no | N=1 |
NEOADJUVANT THERAPY | t test | N=4 | yes | N=3 | no | N=1 |
Time to Death | Duration (Months) | 0.1-210.9 (median=14.8) |
censored | N = 164 | |
death | N = 116 | |
Significant markers | N = 2 | |
associated with shorter survival | 2 | |
associated with longer survival | 0 |
AGE | Mean (SD) | 61.38 (12) |
Significant markers | N = 4 | |
pos. correlated | 4 | |
neg. correlated | 0 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
SLC35D3 | 0.3014 | 2.369e-07 | 0.00414 |
XKR6 | 0.2843 | 1.161e-06 | 0.0203 |
DES | 0.2803 | 1.667e-06 | 0.0291 |
HAND1 | 0.2781 | 2.025e-06 | 0.0353 |
GENDER | Labels | N |
FEMALE | 78 | |
MALE | 205 | |
Significant markers | N = 8 | |
Higher in MALE | 5 | |
Higher in FEMALE | 3 |
T(pos if higher in 'MALE') | ttestP | Q | AUC | |
---|---|---|---|---|
KIF4B | -10.87 | 4.768e-20 | 8.32e-16 | 0.8499 |
LOC96610 | 7.33 | 1.097e-11 | 1.92e-07 | 0.7691 |
FH | 6.68 | 7e-10 | 1.22e-05 | 0.7549 |
FRG1B | -6.64 | 1.55e-09 | 2.71e-05 | 0.7637 |
SLC22A3 | 5.21 | 3.752e-07 | 0.00655 | 0.5934 |
TMEM232 | -5.28 | 5.434e-07 | 0.00948 | 0.7019 |
NLRP2 | 5.04 | 1.474e-06 | 0.0257 | 0.6957 |
TTC21A | 4.88 | 1.933e-06 | 0.0337 | 0.6335 |
PATHOLOGY.T | Mean (SD) | 2.93 (1) |
N | ||
T1 | 20 | |
T2 | 75 | |
T3 | 57 | |
T4 | 98 | |
Significant markers | N = 0 |
PATHOLOGY.N | Mean (SD) | 1.03 (0.96) |
N | ||
N0 | 94 | |
N1 | 31 | |
N2 | 93 | |
N3 | 4 | |
Significant markers | N = 5 | |
pos. correlated | 5 | |
neg. correlated | 0 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
SLC47A2 | 0.3503 | 8.254e-08 | 0.00144 |
ESRRA | 0.3181 | 1.305e-06 | 0.0228 |
AVPI1 | 0.3141 | 1.795e-06 | 0.0313 |
FGD2 | 0.3138 | 1.845e-06 | 0.0322 |
TMCO4 | 0.3095 | 2.592e-06 | 0.0453 |
TUMOR.STAGE | Mean (SD) | 3.3 (0.97) |
N | ||
Stage 1 | 14 | |
Stage 2 | 46 | |
Stage 3 | 38 | |
Stage 4 | 147 | |
Significant markers | N = 1 | |
pos. correlated | 1 | |
neg. correlated | 0 |
SpearmanCorr | corrP | Q | |
---|---|---|---|
LOC400657 | 0.2967 | 2.28e-06 | 0.0398 |
2 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.
RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N |
NO | 75 | |
YES | 208 | |
Significant markers | N = 2 | |
Higher in YES | 1 | |
Higher in NO | 1 |
T(pos if higher in 'YES') | ttestP | Q | AUC | |
---|---|---|---|---|
ZCCHC17 | -5.43 | 2.816e-07 | 0.00492 | 0.7006 |
NEAT1 | 5.23 | 4.465e-07 | 0.00779 | 0.6804 |
NEOADJUVANT.THERAPY | Labels | N |
NO | 45 | |
YES | 238 | |
Significant markers | N = 4 | |
Higher in YES | 3 | |
Higher in NO | 1 |
-
Expresson data file = HNSC.meth.for_correlation.filtered_data.txt
-
Clinical data file = HNSC.clin.merged.picked.txt
-
Number of patients = 283
-
Number of genes = 17460
-
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.