Uterine Corpus Endometrioid Carcinoma: Association of mutation, copy number alteration, and subtype markers with pathways
Maintained by Spring Yingchun Liu (Dana-Farber Cancer Institute)
Overview
Introduction

This pipeline maps genes, with mutation or copy number alteration AND this alteration is highly correlated with mRNA expression, to pathways curated in the KEGG and BIOCARTA databases. It identifies pathways significantly enriched with these genes. The pipeline also identifies pathways significantly enriched with marker genes of each expression subtype of cancer.

genes with mutation: identified by the Mutation_Significance pipeline

genes with copy number alteration: identified by the CopyNumber_Gistic2 pipeline

correlation between copy number and mRNA expression: identified by the Correlate_CopyNumber_vs_mRNA pipeline

marker genes and expression subtypes: identified by the mRNAConsensusClustering pipeline

Summary

There are 210 genes with significant mutation (Q value <= 0.1) and 386 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 1241 for subtype 1, 1241 for subtype 2, 1241 for subtype 3. Pathways significantly enriched with these genes (Q value <= 0.01) are identified :

8 pathways significantly enriched with genes with copy number alteration or mutation.

11 pathways significantly enriched with marker genes of gene expression subtype 1

0 pathways significantly enriched with marker genes of gene expression subtype 2

4 pathways significantly enriched with marker genes of gene expression subtype 3

Results
The top five pathways enriched with genes with copy number alteration or mutation

Table 1. Get Full Table Top Pathways enriched with genes with copy number alteration or mutation. Nof Genes : No. of genes in this pathway. Nof CNV_Mut : No. of genes with copy number alteration or mutation in this pathway. Enrichment , P value and Q value : See Methods & Data below. CNV_Mut Genes in Pathway: genes with copy number alteration or mutation in this pathway.

Pathway | Nof Genes | Nof CNV_Mut | Enrichment | P value | Q value
--- | --- | --- | --- | --- | ---
BIOCARTA_ETS_PATHWAY | 18 | 6 | 3.6 | 0 | 0.0021
KEGG_ENDOMETRIAL_CANCER | 52 | 9 | 2.6 | 0 | 0.0021
BIOCARTA_HIVNEF_PATHWAY | 56 | 8 | 2.3 | 0.0002 | 0.0067
BIOCARTA_RACCYCD_PATHWAY | 26 | 6 | 3 | 0.0001 | 0.0067
BIOCARTA_TNFR1_PATHWAY | 29 | 6 | 2.9 | 0.0001 | 0.0067

List of CNV_Mut genes in this pathway

E2F1,HRAS,E2F4,RBL2,SIN3A,ETV3

List of CNV_Mut genes in this pathway

HRAS,CASP9,ILK,CCND1,ERBB2,CDH1,APC,RAF1,NRAS

List of CNV_Mut genes in this pathway

BAG4,CASP9,CASP8,CASP2,TRAF2,MAP3K1,RASA1,TRADD

List of CNV_Mut genes in this pathway

E2F1,HRAS,CCNE1,RAC1,RAF1,CCND1

List of CNV_Mut genes in this pathway

TRAF2,BAG4,MAP3K1,CASP8,CASP2,TRADD

The top five pathways enriched with marker genes of gene expression subtype 1

Table 2. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 1 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 1 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 1 in this pathway

Pathway | Nof Genes | Nof Marker | Enrichment | P value | Q value
--- | --- | --- | --- | --- | ---
KEGG_CELL_CYCLE | 128 | 30 | 2.2 | 0 | 0
KEGG_OOCYTE_MEIOSIS | 114 | 19 | 1.6 | 0 | 0.0007
KEGG_PATHWAYS_IN_CANCER | 328 | 38 | 1.1 | 0 | 0.0007
BIOCARTA_CELLCYCLE_PATHWAY | 23 | 8 | 2.7 | 0 | 0.0012
KEGG_DNA_REPLICATION | 36 | 9 | 2.2 | 0.0001 | 0.0052

List of marker genes for gene expression subtype 1 in this pathway

DBF4,TTK,PTTG2,PTTG1,CCNA1,CCNA2,RBL1,ANAPC4,SKP2,ORC1L,CHEK1,ANAPC11,CDC20,PLK1,E2F1,CCNE1,CDC45L,CDC7,CDC2,CCNH,MCM2,MCM4,CDK2,MCM6,BUB1B,GADD45A,BUB1,CDC25C,CCNB1,CCNB2

List of marker genes for gene expression subtype 1 in this pathway

PTTG2,PTTG1,PGR,SGOL1,ANAPC4,ANAPC11,FBXO5,CDC20,PLK1,CCNE1,CDC2,AKR1B1,CDK2,CALML3,BUB1,CDC25C,CCNB1,RPS6KA6,CCNB2

List of marker genes for gene expression subtype 1 in this pathway

HRAS,CCNA1,SKP2,CTNNA2,VEGFB,LAMC2,LAMB1,FH,BMP4,BMP2,TCF7,FGF8,CCNE1,FGF3,AKR1B1,CTBP2,RAD51,BIRC5,FZD3,NRAS,PTCH1,TCEB1,FGF19,STK36,FGF12,MMP2,WNT6,RET,FGF20,WNT5A,FGFR3,GRB2,AXIN2,E2F1,LEF1,CDK2,EGLN1,FZD10

List of marker genes for gene expression subtype 1 in this pathway

E2F1,CDC2,CCNH,RBL1,CDK2,CCNB1,CCNE1,CCNA1

List of marker genes for gene expression subtype 1 in this pathway

POLA2,FEN1,MCM2,RNASEH2A,MCM4,MCM6,RFC3,RFC4,RFC2

The top five pathways enriched with marker genes of gene expression subtype 2

Table 3. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 2 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 2 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 2 in this pathway

Pathway | Nof Genes | Nof Marker | Enrichment | P value | Q value
--- | --- | --- | --- | --- | ---
WNT_SIGNALING | 89 | 6 | 2.9 | 0.0001 | 0.046
KEGG_BASAL_CELL_CARCINOMA | 55 | 4 | 3 | 0.0014 | 0.23
BIOCARTA_NO2IL12_PATHWAY | 17 | 2 | 3.7 | 0.0097 | 0.4
BIOCARTA_TOB1_PATHWAY | 21 | 2 | 3.6 | 0.012 | 0.4
BIOCARTA_CTLA4_PATHWAY | 21 | 2 | 3.6 | 0.011 | 0.4

List of marker genes for gene expression subtype 2 in this pathway

WNT4,WNT6,WNT11,ACTB,FZD7,KREMEN1

List of marker genes for gene expression subtype 2 in this pathway

WNT4,WNT6,WNT11,FZD7

List of marker genes for gene expression subtype 2 in this pathway

CD3D,CXCR3

List of marker genes for gene expression subtype 2 in this pathway

CD3D,TOB1

List of marker genes for gene expression subtype 2 in this pathway

CD3D,CTLA4

The top five pathways enriched with marker genes of gene expression subtype 3

Table 4. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 3 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 3 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 3 in this pathway

Pathway | Nof Genes | Nof Marker | Enrichment | P value | Q value
--- | --- | --- | --- | --- | ---
KEGG_CELL_CYCLE | 128 | 19 | 1.9 | 0 | 0.0003
KEGG_CELL_ADHESION_MOLECULES_CAMS | 134 | 17 | 1.6 | 0 | 0.0043
KEGG_TYPE_I_DIABETES_MELLITUS | 44 | 9 | 2.4 | 0 | 0.0043
KEGG_GRAFT_VERSUS_HOST_DISEASE | 42 | 8 | 2.4 | 0.0001 | 0.0098
KEGG_OOCYTE_MEIOSIS | 114 | 14 | 1.6 | 0.0002 | 0.016

List of marker genes for gene expression subtype 3 in this pathway

PTTG2,PTTG1,CDKN2A,ANAPC4,ESPL1,CDC20,CDKN1C,E2F1,CCNE1,MCM2,RB1,MCM4,MDM2,BUB1B,GADD45B,BUB1,CDC25C,CDC25A,CDC25B

List of marker genes for gene expression subtype 3 in this pathway

L1CAM,HLA-DPA1,HLA-DRA,ITGAL,ITGB2,HLA-DRB5,HLA-DPB1,CLDN6,HLA-DMB,HLA-DMA,PDCD1,SDC1,CD2,SELPLG,PTPRC,NLGN1,NLGN2

List of marker genes for gene expression subtype 3 in this pathway

FASLG,HLA-DMB,HLA-DMA,HLA-DRB5,HLA-DPB1,GAD1,ICA1,HLA-DPA1,HLA-DRA

List of marker genes for gene expression subtype 3 in this pathway

FASLG,HLA-DMB,HLA-DMA,HLA-DRB5,HLA-DPB1,HLA-DPA1,KLRC1,HLA-DRA

List of marker genes for gene expression subtype 3 in this pathway

PTTG2,AURKA,PTTG1,PGR,ANAPC4,ESPL1,CDC20,CCNE1,CALML3,BUB1,CALML6,CDC25C,RPS6KA6,ADCY9

Methods & Data
Enrichment

Let genes with copy number alteration or mutation be query genes. Let marker genes of specific identified subtypes be query genes. The Enrichment is calculated as:

- Enrichment = log2 (# of query genes in the pathway/# No of query genes) - log2 (# of genes in the pathway/# of human genes)

P value

The statistical signficance of the pathways that are enriched with genes with copy number alteration or mutation, and the pathways that are enriched with markers genes of specific identified subtypes is measured by P value.

- P value = Fisher exact P value

Q value

The Q value is for adjusting P value for multiple testing. A public available R package is used to calculate the Q value.

Download Results

This is an experimental feature. Location of data archives could not be determined.

References
[1] Qi Zheng, GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis, Nucleic Acids Res. 36(issue suppl 2):W358-W363 (2008)
Meta

- Maintainer = Spring Yingchun Liu

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