Gene Expression Analysis Of Breast Cancer

Ángela Garcinuño Feliciano, Magdalena Paulina Flaszyńska, Natali Sakurako Baba Jensen, Marios Topalis, Alena Schwerin

Introduction

  • Breast Cancer Subtypes: Healthy, Basal, Her2, Luminal A, Luminal B
    subtype  n
1   Healthy 11
2     Basal 41
3      Her2 30
4 Luminal A 29
5 Luminal B 30
  • We consider 26468 genes and 141 samples.

  • Differential Gene Expression Analysis

    • Identify Enriched Pathways

Data

  • Gene Expression Matrix
          GSM1116084 GSM1116085 GSM1116086
1007_s_at    9.47065    9.67440   10.20800
1053_at      8.36311    8.72194    7.78601
117_at       5.95426    7.02523    6.39671
1294_at      6.02119    7.24581    6.85310
1316_at      3.22997    3.29352    3.26204
  • Phenotype (Sample) Metadata
               diagnosis subtype
GSM1116084 Breast cancer   Basal
GSM1116085 Breast cancer   Basal
  • Feature (Gene) Metadata
        Gene.Symbol                                  Gene.Title ENTREZ_GENE_ID
1053_at        RFC2 replication factor C (activator 1) 2, 40kDa           5982

PCA Plot of Expression Data

Patterns of gene expression within one subtype differ generally from other subtypes.

Differential Expression Results


Comparison Down NotSig Up
Basal vs Her2 4,214 17,359 4,895
Basal vs LumA 7,551 10,767 8,150
Her2 vs LumA 5,390 15,936 5,142
LumA vs LumB 3,478 19,817 3,173

Most Significant Pathways - Basal

BP_df <- msigdbr(species = "human", category = "C5", subcategory = "BP")
pathways <- split(BP_df$gene_symbol, f = BP_df$gs_name)
fgseaRes <- fgseaMultilevel(
  pathways = pathways,
  stats    = stats,
  minSize  = 15,
  maxSize  = 500)


Pathway padj NES leadingEdge
CHROMOSOME_SEGREGATION 2.002e-36 3.218 <chr[108]>
ORGANELLE_FISSION 1.392e-35 2.969 <chr[127]>
NUCLEAR_CHROMOSOME SEGREGATION 5,312e-34 3.245 <chr[91]>
MITOTIC_NUCLEAR_DIVISION 2.115e-29 3.066 <chr[93]>
SISTER_CHROMATID_SEGREGATION 1.402e-28 3.242 <chr[76]>

Leading Edge Genes in Top 5 Pathways - Basal

Path 1 Path 2 Path 3 Path 4 Path 5
KIF2C KIF2C KIF2C KIF2C KIF2C
AURKB AURKB AURKB AURKB AURKB
KIF14 KIF14 KIF14 KIF14 KIF14
CEP55 CEP55 CEP55 CEP55 CEP55
BUB1 BUB1 BUB1 BUB1 BUB1
CDC20 CDC20 CDC20 CDC20 CDC20
TTK TTK TTK TTK TTK
FAM83D TPX2 FAM83D TPX2 CENPF
MKI67 ASPM CENPF MKI67 CDCA5
CENPF MKI67 CDCA5 CENPF NDC80

Network modules (Louvain detection)

Top 40 differentially expressed genes

ORA analysis for biological interpretation

symbol direction module module_label
PIGR Upregulated 1 NEUTROPHIL DEGRANULATION
ADIPOQ Upregulated 8 TRANSCRIPTIONAL REGULATION BY TP53
COL11A1 Downregulated 6 RRNA PROCESSING
COL10A1 Downregulated 6 RRNA PROCESSING
SCARA5 Upregulated 6 RRNA PROCESSING
RBP4 Upregulated 6 RRNA PROCESSING
LEP Upregulated 8 TRANSCRIPTIONAL REGULATION BY TP53
CXCL10 Downregulated 2 SIGNALING BY GPCR
VCAN Downregulated 6 RRNA PROCESSING
RRM2 Downregulated 3 CELL CYCLE MITOTIC
PLIN1 Upregulated 8 TRANSCRIPTIONAL REGULATION BY TP53
TOP2A Downregulated 3 CELL CYCLE MITOTIC
S100P Downregulated 1 NEUTROPHIL DEGRANULATION
TPD52 Downregulated 5 ASPARAGINE N LINKED GLYCOSYLATION
SH3GL3 Upregulated 5 ASPARAGINE N LINKED GLYCOSYLATION
CHRDL1 Upregulated 6 RRNA PROCESSING
HSP90AB1 Downregulated 7 RHO GTPASE CYCLE
COL12A1 Downregulated 6 RRNA PROCESSING
KRT14 Upregulated 6 RRNA PROCESSING
INHBA Downregulated 8 TRANSCRIPTIONAL REGULATION BY TP53
OXTR Upregulated 2 SIGNALING BY GPCR
ABCA8 Upregulated 9 CLASS I MHC MEDIATED ANTIGEN PROCESSING PRESENTATION
MMP11 Downregulated 6 RRNA PROCESSING
CFD Upregulated 1 NEUTROPHIL DEGRANULATION
SMC4 Downregulated 3 CELL CYCLE MITOTIC
GPD1 Upregulated 4 SLC MEDIATED TRANSMEMBRANE TRANSPORT
ENO1 Downregulated 3 CELL CYCLE MITOTIC
CD300LG Upregulated 6 RRNA PROCESSING
P4HB Downregulated 2 SIGNALING BY GPCR
LPL Upregulated 6 RRNA PROCESSING
FUS Downregulated 11 PROCESSING OF CAPPED INTRON CONTAINING PRE MRNA
ESRP1 Downregulated 2 SIGNALING BY GPCR
EIF5A Downregulated 1 NEUTROPHIL DEGRANULATION
ATAD2 Downregulated 8 TRANSCRIPTIONAL REGULATION BY TP53
CXCL9 Downregulated 2 SIGNALING BY GPCR
NTRK2 Upregulated 2 SIGNALING BY GPCR
BTNL9 Upregulated 6 RRNA PROCESSING
CIDEC Upregulated 6 RRNA PROCESSING
MYBPC1 Upregulated 7 RHO GTPASE CYCLE
FABP4 Upregulated 8 TRANSCRIPTIONAL REGULATION BY TP53

Conclusion

  • PCA plot

  • Differential Gene Expression Analysis:

    • Basal vs Luminal A: cell division
    • Cancer vs Healthy: immune response disruption, cell division enhancement, transcription deregulation