Correlation between miRseq expression and clinical features
Bladder Urothelial Carcinoma (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C1Q23X7Q
Maintained by Juok Cho (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between miRseq expression and clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1Q23X7Q
Overview
Introduction

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

Summary

Testing the association between 580 genes and 9 clinical features across 137 samples, statistically thresholded by Q value < 0.05, 3 clinical features related to at least one genes.

  • 2 genes correlated to 'DISTANT.METASTASIS'.

    • HSA-MIR-216B ,  HSA-MIR-1179

  • 1 gene correlated to 'LYMPH.NODE.METASTASIS'.

    • HSA-MIR-3136

  • 1 gene correlated to 'NEOPLASM.DISEASESTAGE'.

    • HSA-MIR-372

  • No genes correlated to 'Time to Death', 'AGE', 'GENDER', 'KARNOFSKY.PERFORMANCE.SCORE', 'NUMBERPACKYEARSSMOKED', and 'NUMBER.OF.LYMPH.NODES'.

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=0        
GENDER t test   N=0        
KARNOFSKY PERFORMANCE SCORE Spearman correlation test   N=0        
NUMBERPACKYEARSSMOKED Spearman correlation test   N=0        
DISTANT METASTASIS ANOVA test N=2        
LYMPH NODE METASTASIS ANOVA test N=1        
NUMBER OF LYMPH NODES Spearman correlation test   N=0        
NEOPLASM DISEASESTAGE ANOVA test N=1        
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) 0.1-131.2 (median=7)
  censored N = 95
  death N = 35
     
  Significant markers N = 0
Clinical variable #2: 'AGE'

No gene related to 'AGE'.

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

AGE Mean (SD) 67.57 (11)
  Significant markers N = 0
Clinical variable #3: 'GENDER'

No gene related to 'GENDER'.

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

GENDER Labels N
  FEMALE 35
  MALE 102
     
  Significant markers N = 0
Clinical variable #4: 'KARNOFSKY.PERFORMANCE.SCORE'

No gene related to 'KARNOFSKY.PERFORMANCE.SCORE'.

Table S4.  Basic characteristics of clinical feature: 'KARNOFSKY.PERFORMANCE.SCORE'

KARNOFSKY.PERFORMANCE.SCORE Mean (SD) 78.21 (16)
  Significant markers N = 0
Clinical variable #5: 'NUMBERPACKYEARSSMOKED'

No gene related to 'NUMBERPACKYEARSSMOKED'.

Table S5.  Basic characteristics of clinical feature: 'NUMBERPACKYEARSSMOKED'

NUMBERPACKYEARSSMOKED Mean (SD) 36.79 (23)
  Significant markers N = 0
Clinical variable #6: 'DISTANT.METASTASIS'

2 genes related to 'DISTANT.METASTASIS'.

Table S6.  Basic characteristics of clinical feature: 'DISTANT.METASTASIS'

DISTANT.METASTASIS Labels N
  M0 80
  M1 5
  MX 51
     
  Significant markers N = 2
List of 2 genes differentially expressed by 'DISTANT.METASTASIS'

Table S7.  Get Full Table List of 2 genes differentially expressed by 'DISTANT.METASTASIS'

ANOVA_P Q
HSA-MIR-216B 5.765e-07 0.000334
HSA-MIR-1179 9.766e-07 0.000565

Figure S1.  Get High-res Image As an example, this figure shows the association of HSA-MIR-216B to 'DISTANT.METASTASIS'. P value = 5.76e-07 with ANOVA analysis.

Clinical variable #7: 'LYMPH.NODE.METASTASIS'

One gene related to 'LYMPH.NODE.METASTASIS'.

Table S8.  Basic characteristics of clinical feature: 'LYMPH.NODE.METASTASIS'

LYMPH.NODE.METASTASIS Labels N
  N0 77
  N1 14
  N2 28
  N3 5
  NX 10
     
  Significant markers N = 1
List of one gene differentially expressed by 'LYMPH.NODE.METASTASIS'

Table S9.  Get Full Table List of one gene differentially expressed by 'LYMPH.NODE.METASTASIS'

ANOVA_P Q
HSA-MIR-3136 8.066e-06 0.00468

Figure S2.  Get High-res Image As an example, this figure shows the association of HSA-MIR-3136 to 'LYMPH.NODE.METASTASIS'. P value = 8.07e-06 with ANOVA analysis.

Clinical variable #8: 'NUMBER.OF.LYMPH.NODES'

No gene related to 'NUMBER.OF.LYMPH.NODES'.

Table S10.  Basic characteristics of clinical feature: 'NUMBER.OF.LYMPH.NODES'

NUMBER.OF.LYMPH.NODES Mean (SD) 1.86 (3.7)
  Significant markers N = 0
Clinical variable #9: 'NEOPLASM.DISEASESTAGE'

One gene related to 'NEOPLASM.DISEASESTAGE'.

Table S11.  Basic characteristics of clinical feature: 'NEOPLASM.DISEASESTAGE'

NEOPLASM.DISEASESTAGE Labels N
  STAGE I 1
  STAGE II 37
  STAGE III 45
  STAGE IV 49
     
  Significant markers N = 1
List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

Table S12.  Get Full Table List of one gene differentially expressed by 'NEOPLASM.DISEASESTAGE'

ANOVA_P Q
HSA-MIR-372 4.358e-05 0.0253

Figure S3.  Get High-res Image As an example, this figure shows the association of HSA-MIR-372 to 'NEOPLASM.DISEASESTAGE'. P value = 4.36e-05 with ANOVA analysis.

Methods & Data
Input

  • Expresson data file = BLCA-TP.miRseq_RPKM_log2.txt

  • Clinical data file = BLCA-TP.clin.merged.picked.txt

  • Number of patients = 137

  • Number of genes = 580

  • Number of clinical features = 9

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.

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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