Stomach Adenocarcinoma: Correlation between miRseq expression and clinical features
Maintained by Juok Cho (Broad Institute)
Overview
Introduction

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

Summary

Testing the association between 533 genes and 10 clinical features across 150 samples, statistically thresholded by Q value < 0.05, 5 clinical features related to at least one genes.

- 2 genes correlated to 'AGE'.

- HSA-MIR-183 , HSA-MIR-96

- 1 gene correlated to 'HISTOLOGICAL.TYPE'.

- HSA-MIR-33A

- 1 gene correlated to 'PATHOLOGY.T'.

- HSA-MIR-200B

- 6 genes correlated to 'RADIATIONS.RADIATION.REGIMENINDICATION'.

- HSA-MIR-3150 , HSA-MIR-23A , HSA-MIR-548F-1 , HSA-MIR-559 , HSA-MIR-1237 , ...

- 1 gene correlated to 'NEOADJUVANT.THERAPY'.

- HSA-MIR-514-1

- No genes correlated to 'Time to Death', 'GENDER', 'PATHOLOGY.N', 'PATHOLOGICSPREAD(M)', and 'TUMOR.STAGE'.

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 |
--- | --- | --- | --- | --- | --- | ---
Time to Death | Cox regression test | N=0 |  |  |  |
AGE | Spearman correlation test | N=2 | older | N=2 | younger | N=0
GENDER | t test | N=0 |  |  |  |
HISTOLOGICAL TYPE | ANOVA test | N=1 |  |  |  |
PATHOLOGY T | Spearman correlation test | N=1 | higher pT | N=0 | lower pT | N=1
PATHOLOGY N | Spearman correlation test | N=0 |  |  |  |
PATHOLOGICSPREAD(M) | ANOVA test | N=0 |  |  |  |
TUMOR STAGE | Spearman correlation test | N=0 |  |  |  |
RADIATIONS RADIATION REGIMENINDICATION | t test | N=6 | yes | N=6 | no | N=0
NEOADJUVANT THERAPY | t test | N=1 | yes | N=1 | no | N=0

Clinical variable #1: 'Time to Death'

No gene related to 'Time to Death'.

Table S1. Basic characteristics of clinical feature: 'Time to Death'

Time to Death | Duration (Months) | 0.1-72.2 (median=3)
| censored | N = 82
| death | N = 15
| Significant markers | N = 0

Clinical variable #2: 'AGE'

2 genes related to 'AGE'.

Table S2. Basic characteristics of clinical feature: 'AGE'

AGE | Mean (SD) | 67.8 (11)
| Significant markers | N = 2
| pos. correlated | 2
| neg. correlated | 0

List of 2 genes significantly correlated to 'AGE' by Spearman correlation test

Table S3. Get Full Table List of 2 genes significantly correlated to 'AGE' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
HSA-MIR-183 | 0.336 | 4.083e-05 | 0.0218
HSA-MIR-96 | 0.3354 | 4.227e-05 | 0.0225

Figure S1. Get High-res Image As an example, this figure shows the association of HSA-MIR-183 to 'AGE'. P value = 4.08e-05 with Spearman correlation analysis. The straight line presents the best linear regression.

Clinical variable #3: 'GENDER'

No gene related to 'GENDER'.

Table S4. Basic characteristics of clinical feature: 'GENDER'

GENDER | Labels | N
| FEMALE | 59
| MALE | 91
| Significant markers | N = 0

Clinical variable #4: 'HISTOLOGICAL.TYPE'

One gene related to 'HISTOLOGICAL.TYPE'.

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

HISTOLOGICAL.TYPE | Labels | N
| STOMACH ADENOCARCINOMA - DIFFUSE TYPE | 14
| STOMACH ADENOCARCINOMA - NOT OTHERWISE SPECIFIED (NOS) | 85
| STOMACH INTESTINAL ADENOCARCINOMA - MUCINOUS TYPE | 7
| STOMACH INTESTINAL ADENOCARCINOMA - PAPILLARY TYPE | 3
| STOMACH INTESTINAL ADENOCARCINOMA - TUBULAR TYPE | 10
| STOMACH INTESTINAL ADENOCARCINOMA - TYPE NOT OTHERWISE SPECIFIED (NOS) | 26
| Significant markers | N = 1

List of one gene differentially expressed by 'HISTOLOGICAL.TYPE'

Table S6. Get Full Table List of one gene differentially expressed by 'HISTOLOGICAL.TYPE'

| ANOVA_P | Q
--- | --- | ---
HSA-MIR-33A | 2.187e-05 | 0.0117

Figure S2. Get High-res Image As an example, this figure shows the association of HSA-MIR-33A to 'HISTOLOGICAL.TYPE'. P value = 2.19e-05 with ANOVA analysis.

Clinical variable #5: 'PATHOLOGY.T'

One gene related to 'PATHOLOGY.T'.

Table S7. Basic characteristics of clinical feature: 'PATHOLOGY.T'

PATHOLOGY.T | Mean (SD) | 2.64 (0.77)
|  | N
| T1 | 6
| T2 | 51
| T3 | 55
| T4 | 17
| Significant markers | N = 1
| pos. correlated | 0
| neg. correlated | 1

List of one gene significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

Table S8. Get Full Table List of one gene significantly correlated to 'PATHOLOGY.T' by Spearman correlation test

| SpearmanCorr | corrP | Q
--- | --- | --- | ---
HSA-MIR-200B | -0.3774 | 1.037e-05 | 0.00553

Figure S3. Get High-res Image As an example, this figure shows the association of HSA-MIR-200B to 'PATHOLOGY.T'. P value = 1.04e-05 with Spearman correlation analysis.

Clinical variable #6: 'PATHOLOGY.N'

No gene related to 'PATHOLOGY.N'.

Table S9. Basic characteristics of clinical feature: 'PATHOLOGY.N'

PATHOLOGY.N | Mean (SD) | 1.04 (0.94)
|  | N
| N0 | 43
| N1 | 54
| N2 | 22
| N3 | 13
| Significant markers | N = 0

Clinical variable #7: 'PATHOLOGICSPREAD(M)'

No gene related to 'PATHOLOGICSPREAD(M)'.

Table S10. Basic characteristics of clinical feature: 'PATHOLOGICSPREAD(M)'

PATHOLOGICSPREAD(M) | Labels | N
| M0 | 130
| M1 | 14
| MX | 6
| Significant markers | N = 0

Clinical variable #8: 'TUMOR.STAGE'

No gene related to 'TUMOR.STAGE'.

Table S11. Basic characteristics of clinical feature: 'TUMOR.STAGE'

TUMOR.STAGE | Mean (SD) | 2.52 (1)
|  | N
| Stage 1 | 24
| Stage 2 | 35
| Stage 3 | 38
| Stage 4 | 25
| Significant markers | N = 0

Clinical variable #9: 'RADIATIONS.RADIATION.REGIMENINDICATION'

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

Table S12. Basic characteristics of clinical feature: 'RADIATIONS.RADIATION.REGIMENINDICATION'

RADIATIONS.RADIATION.REGIMENINDICATION | Labels | N
| NO | 5
| YES | 145
| Significant markers | N = 6
| Higher in YES | 6
| Higher in NO | 0

List of 6 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

Table S13. Get Full Table List of 6 genes differentially expressed by 'RADIATIONS.RADIATION.REGIMENINDICATION'

| T(pos if higher in 'YES') | ttestP | Q | AUC
--- | --- | --- | --- | ---
HSA-MIR-3150 | 7.78 | 2.648e-09 | 1.25e-06 | 0.8362
HSA-MIR-23A | 9.26 | 3.316e-07 | 0.000156 | 0.8869
HSA-MIR-548F-1 | 8.02 | 1.133e-06 | 0.000532 | 0.9136
HSA-MIR-559 | 7.74 | 6.805e-06 | 0.00319 | 0.8866
HSA-MIR-1237 | 4.97 | 3.094e-05 | 0.0145 | 0.7649
HSA-MIR-548D-2 | 5.9 | 4.121e-05 | 0.0192 | 0.8594

Figure S4. Get High-res Image As an example, this figure shows the association of HSA-MIR-3150 to 'RADIATIONS.RADIATION.REGIMENINDICATION'. P value = 2.65e-09 with T-test analysis.

Clinical variable #10: 'NEOADJUVANT.THERAPY'

One gene related to 'NEOADJUVANT.THERAPY'.

Table S14. Basic characteristics of clinical feature: 'NEOADJUVANT.THERAPY'

NEOADJUVANT.THERAPY | Labels | N
| NO | 10
| YES | 140
| Significant markers | N = 1
| Higher in YES | 1
| Higher in NO | 0

List of one gene differentially expressed by 'NEOADJUVANT.THERAPY'

Table S15. Get Full Table List of one gene differentially expressed by 'NEOADJUVANT.THERAPY'

| T(pos if higher in 'YES') | ttestP | Q | AUC
--- | --- | --- | --- | ---
HSA-MIR-514-1 | 5.29 | 2.686e-05 | 0.0142 | 0.7886

Figure S5. Get High-res Image As an example, this figure shows the association of HSA-MIR-514-1 to 'NEOADJUVANT.THERAPY'. P value = 2.69e-05 with T-test analysis.

Methods & Data
Input

- Expresson data file = STAD.miRseq_RPKM_log2.txt

- Clinical data file = STAD.clin.merged.picked.txt

- Number of patients = 150

- Number of genes = 533

- Number of clinical features = 10

Survival analysis

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

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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

References
[1] Andersen and Gill, Cox's regression model for counting processes, a large sample study, Annals of Statistics 10(4):1100-1120 (1982)
[2] Spearman, C, The proof and measurement of association between two things, Amer. J. Psychol 15:72-101 (1904)
[3] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[4] Howell, D, Statistical Methods for Psychology. (5th ed.), Duxbury Press:324-5 (2002)
[5] 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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