Lung Squamous Cell Carcinoma: Association of mutation, copy number alteration, and subtype markers with pathways<BR>(primary solid tumor cohort)

Lung Squamous Cell Carcinoma: Association of mutation, copy number alteration, and subtype markers with pathways
(primary solid tumor cohort)

Maintained by Spring Yingchun Liu (Broad 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 114 genes with significant mutation (Q value <= 0.1) and 225 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 1163 for subtype 1, 1163 for subtype 2, 1163 for subtype 3. Pathways significantly enriched with these genes (Q value <= 0.01) are identified :

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

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

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

6 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
KEGG_OLFACTORY_TRANSDUCTION	389	27	2.1	0	0
KEGG_UBIQUITIN_MEDIATED_PROTEOLYSIS	137	12	2.5	0	0.0003
KEGG_SPLICEOSOME	126	8	2.1	0.0005	0.041
KEGG_PROTEIN_EXPORT	24	4	3.4	0.0005	0.041
BIOCARTA_G1_PATHWAY	28	4	3.1	0.001	0.066

List of CNV_Mut genes in this pathway

OR2T2,OR2T8,OR4N2,OR10R2,OR2AK2,OR8K3,OR51B2,OR2L13,OR2T33,OR2M7,OR5AC2,OR2T12,OR52J3,OR8H1,OR2A5,OR10A4,OR6F1,OR2G6,OR4M1,OR5M9,OR5AS1,OR14A16,OR6K3,OR6K2,OR4C11,OR10G8,OR5K1

List of CNV_Mut genes in this pathway

CUL3,CUL5,CUL1,SKP2,UBE2D2,FBXO4,UBE2F,UBE3C,FBXW11,PARK2,BIRC2,CUL4A

List of CNV_Mut genes in this pathway

SNRPA1,AQR,SLU7,HNRNPC,SNRPF,PPIE,BCAS2,TXNL4A

List of CNV_Mut genes in this pathway

SRP14,OXA1L,SRP19,SEC61G

List of CNV_Mut genes in this pathway

CDKN2A,TFDP1,SKP2,RB1

+ 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_GLUTATHIONE_METABOLISM	50	12	2.2	0	0.0017
KEGG_DRUG_METABOLISM_CYTOCHROME_P450	72	14	1.9	0	0.0022
KEGG_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450	70	13	1.8	0	0.005
KEGG_AXON_GUIDANCE	129	15	1.2	0.0023	0.15
KEGG_DILATED_CARDIOMYOPATHY	92	12	1.4	0.0022	0.15

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

GSTM5,GSTM1,GPX2,GSTM2,GSR,GSTM3,GCLC,GSTO1,GSTA3,GSTA4,GSTA5,GGT7

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

CYP2C19,GSTM5,GSTM1,GSTM2,GSTM3,ALDH3B2,ALDH3B1,ADH5,ALDH3A1,FMO3,GSTO1,GSTA3,GSTA4,GSTA5

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

CYP2C19,GSTM5,GSTM1,GSTM2,GSTM3,ALDH3B2,ALDH3B1,ADH5,ALDH3A1,GSTO1,GSTA3,GSTA4,GSTA5

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

PLXNA1,PLXNB1,EFNB2,MAPK1,EPHB3,EPHA1,RGS3,SEMA3F,PAK1,SEMA4G,NCK1,SEMA4B,CHP,FYN,GSK3B

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

ADCY8,ADCY6,PRKX,SGCG,MYL3,CACNB2,ITGB5,TPM4,SLC8A1,ITGA2,ATP2A2,ITGA7

+ 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
BIOCARTA_AGR_PATHWAY	36	12	1.9	0	0.0043
KEGG_ENDOCYTOSIS	183	33	1.1	0	0.0043
KEGG_ARRHYTHMOGENIC_RIGHT_VENTRICULAR_CARDIOMYOPATHY_ARVC	76	18	1.5	0	0.0044
KEGG_FOCAL_ADHESION	201	34	0.95	0.0001	0.0072
BIOCARTA_INTRINSIC_PATHWAY	23	8	2	0.0005	0.02

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

ITGB1,PXN,CDC42,PAK1,NRG2,ITGA1,DVL1,LAMA2,MAPK1,LAMA4,PSG1,MAPK8

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

PSD3,HLA-C,HLA-G,HLA-F,ARRB2,ERBB3,ASAP2,ASAP1,ASAP3,SNF8,AP2M1,GIT1,PARD6B,KDR,RABEP1,PIP4K2B,VPS37A,IL8RB,VPS37C,CDC42,BRD8,UNC45A,CXCR4,ADRB1,CHMP1B,IGF1R,HSPA2,SH3GLB1,IL2RG,EHD2,STAMBP,FAM125B,DNM3

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

ACTG1,DES,ACTN1,CACNB2,ITGB3,TCF7L2,ITGB1,ITGB7,CACNA2D1,TCF7,ITGA1,ITGA3,LAMA2,ITGA6,DSG2,ITGA8,ITGA7,DSC2

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

ACTG1,ILK,RAPGEF1,PIK3CG,BRAF,MAPK1,MAPK8,PXN,LAMB4,KDR,LAMA2,LAMA1,LAMA4,PTEN,CCND1,CAPN2,BIRC2,FYN,ACTN1,CAV2,ITGB3,ITGB1,DOCK1,ITGB7,ITGA1,ITGA3,ITGA6,ITGA8,ITGA7,CDC42,PAK1,IGF1R,PIK3R3,COL4A6

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

F12,F10,COL4A6,COL4A5,PROC,FGG,F5,FGA

+ 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_BASAL_CELL_CARCINOMA	55	16	2	0	0.0004
KEGG_WNT_SIGNALING_PATHWAY	151	27	1.3	0	0.0021
KEGG_MELANOGENESIS	102	20	1.4	0	0.0045
KEGG_PATHWAYS_IN_CANCER	328	44	0.86	0.0001	0.0054
BIOCARTA_G1_PATHWAY	28	9	2.1	0.0001	0.0066