Thyroid Adenocarcinoma: Correlation between mRNAseq expression and clinical features<BR>(primary solid tumor cohort)

Thyroid Adenocarcinoma: Correlation between mRNAseq expression and clinical features
(primary solid tumor cohort)

Maintained by Juok Cho (Broad Institute)

Overview

Introduction

This pipeline uses various statistical tests to identify mRNAs whose expression levels correlated to selected clinical features.

Summary

Testing the association between 18015 genes and 5 clinical features across 198 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

83 genes correlated to 'AGE'.

C12ORF52|84934 , EPN3|55040 , GOT2|2806 , KBTBD2|25948 , GPI|2821 , ...

33 genes correlated to 'GENDER'.

DDX3Y|8653 , RPS4Y1|6192 , ZFY|7544 , USP9Y|8287 , KDM5D|8284 , ...

3625 genes correlated to 'HISTOLOGICAL.TYPE'.

FN1|2335 , LDLR|3949 , FAM176A|84141 , ANKLE2|23141 , PTPRE|5791 , ...

38 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

FLJ37543|285668 , C14ORF180|400258 , A2ML1|144568 , LOC440173|440173 , TAS2R43|259289 , ...

25 genes correlated to 'RADIATIONEXPOSURE'.

ZNF804B|219578 , DMPK|1760 , SLC12A1|6557 , FOLR4|390243 , CXORF30|645090 , ...

Results

Overview of the results

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
AGE	Spearman correlation test	N=83	older	N=46	younger	N=37
GENDER	t test	N=33	male	N=13	female	N=20
HISTOLOGICAL TYPE	ANOVA test	N=3625
RADIATIONS RADIATION REGIMENINDICATION	t test	N=38	yes	N=22	no	N=16
RADIATIONEXPOSURE	t test	N=25	yes	N=0	no	N=25

Clinical variable #1: 'AGE'

83 genes related to 'AGE'.

Table S1. Basic characteristics of clinical feature: 'AGE'


AGE	Mean (SD)	46.74 (16)
	Significant markers	N = 83
	pos. correlated	46
	neg. correlated	37

List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

Table S2. Get Full Table List of top 10 genes significantly correlated to 'AGE' by Spearman correlation test

	SpearmanCorr	corrP	Q
C12ORF52\|84934	0.408	2.433e-09	4.38e-05
EPN3\|55040	0.3949	8.517e-09	0.000153
GOT2\|2806	0.3892	1.453e-08	0.000262
KBTBD2\|25948	-0.3806	3.176e-08	0.000572
GPI\|2821	0.3789	3.715e-08	0.000669
GPR173\|54328	-0.3784	4.199e-08	0.000756
MST1P9\|11223	-0.376	4.795e-08	0.000864
PTPN12\|5782	-0.376	4.81e-08	0.000866
HADH\|3033	0.3726	6.458e-08	0.00116
ALDOA\|226	0.3725	6.51e-08	0.00117

Figure S1. Get High-res Image As an example, this figure shows the association of C12ORF52|84934 to 'AGE'. P value = 2.43e-09 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #2: 'GENDER'

33 genes related to 'GENDER'.

Table S3. Basic characteristics of clinical feature: 'GENDER'


GENDER	Labels	N
	FEMALE	146
	MALE	52

	Significant markers	N = 33
	Higher in MALE	13
	Higher in FEMALE	20

List of top 10 genes differentially expressed by 'GENDER'

Table S4. Get Full Table List of top 10 genes differentially expressed by 'GENDER'

	T(pos if higher in 'MALE')	ttestP	Q	AUC
DDX3Y\|8653	72.55	1.046e-99	1.88e-95	1
RPS4Y1\|6192	59.63	6.738e-94	1.21e-89	1
ZFY\|7544	62.73	6.467e-88	1.16e-83	1
USP9Y\|8287	61.51	8.561e-78	1.54e-73	1
KDM5D\|8284	65.97	3.356e-76	6.04e-72	1
UTY\|7404	63.25	3.346e-74	6.03e-70	1
NLGN4Y\|22829	44.85	2.175e-63	3.92e-59	1
PRKY\|5616	27.66	1.737e-62	3.13e-58	0.9982
CYORF15A\|246126	49.43	1.619e-51	2.91e-47	1
CYORF15B\|84663	46.07	3.858e-49	6.95e-45	1

Figure S2. Get High-res Image As an example, this figure shows the association of DDX3Y|8653 to 'GENDER'. P value = 1.05e-99 with T-test analysis.

Clinical variable #3: 'HISTOLOGICAL.TYPE'

3625 genes related to 'HISTOLOGICAL.TYPE'.

Table S5. Basic characteristics of clinical feature: 'HISTOLOGICAL.TYPE'


HISTOLOGICAL.TYPE	Labels	N
	OTHER	7
	THYROID PAPILLARY CARCINOMA - CLASSICAL/USUAL	113
	THYROID PAPILLARY CARCINOMA - FOLLICULAR (>= 99% FOLLICULAR PATTERNED)	58
	THYROID PAPILLARY CARCINOMA - TALL CELL (>= 50% TALL CELL FEATURES)	20

	Significant markers	N = 3625

List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

Table S6. Get Full Table List of top 10 genes differentially expressed by 'HISTOLOGICAL.TYPE'

	ANOVA_P	Q
FN1\|2335	1.749e-29	3.15e-25
LDLR\|3949	1.138e-27	2.05e-23
FAM176A\|84141	4.052e-27	7.3e-23
ANKLE2\|23141	6.008e-27	1.08e-22
PTPRE\|5791	2.186e-26	3.94e-22
TMPRSS6\|164656	3.242e-26	5.84e-22
SFTPB\|6439	7.071e-26	1.27e-21
CREB5\|9586	7.528e-26	1.36e-21
KCNN4\|3783	9.053e-25	1.63e-20
GABRB2\|2561	9.205e-25	1.66e-20

Figure S3. Get High-res Image As an example, this figure shows the association of FN1|2335 to 'HISTOLOGICAL.TYPE'. P value = 1.75e-29 with ANOVA analysis.

Clinical variable #4: 'RADIATIONS.RADIATION.REGIMENINDICATION'

38 genes related to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

Table S7. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'


RADIATIONS.RADIATION.REGIMENINDICATION	Labels	N
	NO	12
	YES	186

	Significant markers	N = 38
	Higher in YES	22
	Higher in NO	16

List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S8. Get Full Table List of top 10 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

	T(pos if higher in 'YES')	ttestP	Q	AUC
FLJ37543\|285668	10.71	2.564e-14	4.6e-10	0.8484
C14ORF180\|400258	8.73	1.291e-12	2.32e-08	0.8645
A2ML1\|144568	8.27	1.664e-10	2.99e-06	0.8168
LOC440173\|440173	7.5	2.426e-09	4.35e-05	0.8936
TAS2R43\|259289	6.77	9.702e-09	0.000174	0.7729
HCFC1\|3054	-8.94	1.695e-08	0.000304	0.8844
HPR\|3250	7.89	4.509e-08	0.000809	0.9041
DNAH14\|127602	-7.75	4.973e-08	0.000892	0.8392
ENPP3\|5169	7.36	1.021e-07	0.00183	0.8383
TMEM20\|159371	7.59	1.353e-07	0.00243	0.8401

Figure S4. Get High-res Image As an example, this figure shows the association of FLJ37543|285668 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.56e-14 with T-test analysis.

Clinical variable #5: 'RADIATIONEXPOSURE'

25 genes related to 'RADIATIONEXPOSURE'.

Table S9. Basic characteristics of clinical feature: 'RADIATIONEXPOSURE'


RADIATIONEXPOSURE	Labels	N
	NO	162
	YES	8

	Significant markers	N = 25
	Higher in YES	0
	Higher in NO	25

List of top 10 genes differentially expressed by 'RADIATIONEXPOSURE'

Table S10. Get Full Table List of top 10 genes differentially expressed by 'RADIATIONEXPOSURE'

	T(pos if higher in 'YES')	ttestP	Q	AUC
ZNF804B\|219578	-17.38	1.064e-32	1.88e-28	0.9667
DMPK\|1760	-10.6	1.848e-18	3.26e-14	0.8287
SLC12A1\|6557	-10.36	3.087e-17	5.45e-13	0.9007
FOLR4\|390243	-9.99	1.262e-15	2.23e-11	0.8889
CXORF30\|645090	-9.59	5.821e-12	1.03e-07	0.9231
ASCL1\|429	-9.01	1.117e-11	1.97e-07	0.8419
C17ORF64\|124773	-8.19	3.835e-11	6.77e-07	0.846
GRIA1\|2890	-8.62	6.718e-11	1.19e-06	0.8359
FAM138F\|641702	-7.58	2.274e-10	4.01e-06	0.8361
LOC127841\|127841	-7.35	1.147e-09	2.02e-05	0.8534

Figure S5. Get High-res Image As an example, this figure shows the association of ZNF804B|219578 to 'RADIATIONEXPOSURE'. P value = 1.06e-32 with T-test analysis.

Methods & Data

Input

Expresson data file = THCA-TP.uncv2.mRNAseq_RSEM_normalized_log2.txt
Clinical data file = THCA-TP.clin.merged.picked.txt
Number of patients = 198
Number of genes = 18015
Number of clinical features = 5

Correlation analysis

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

Student's t-test analysis

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

ANOVA analysis

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

Q value calculation

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.

Download Results

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

References

[1] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)

[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)

[3] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)

[4] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)

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