Table 1.
GEO series utilized for this study.
The table details the disease sample size and microarray/RNA-seq. platform. T2DM: type 2 diabetes mellitus; BC: breast cancer; D: diabetes.
Fig 1.
Flow diagrammatic representation of methodology.
The boxes in green represent analyses, yellow-conditions applied and blue for immediate outcome/ subsequent process step. The pink box indicates the final outcome.
Table 2.
Differential gene expression analysis.
The results show the number of differentially expressed genes (DEGs) for each series analyzed, along with the top 10 most significant up-regulated and down-regulated DEGs.
Fig 2.
Venn diagram analysis for T2DM -adipose tissue and breast adenocarcinoma (BC) samples.
The yellow circle represents DEGs obtained from DEG analysis on T2DM samples and the pink circle represents DEGs from BC samples, similarly. A- The intersection represents DEGs common to T2DM and BC. B- The intersection represents up-regulated DEGs common to both diseases. C- The intersection represents down-regulated DEGs common to both diseases.
Table 3.
The 94 DEGs common to both T2DM and BC are listed. The expression of each of the DEGs in both diseases is also indicated. DEGs: differentially expressed genes; T2DM: type 2 diabetes mellitus; BC: breast cancer.
Fig 3.
Functional and pathway enrichment analyses.
The most significant results are presented from top to bottom. A- Shows the results for GO term biological processes, B- GO term molecular function, and C- GO term cellular component. D- Most significantly results for KEGG pathways.
Fig 4.
Protein- protein interaction network for common DEGs.
All disconnected nodes were removed from the network. The sphere represents node (protein encoded by the gene) and the line depicts interaction. The color of the line is representative of the source of evidence for interaction, including text mining (light green), gene neighborhood (dark green), experimentally determined (magenta), and curated databases (blue). The structure within sphere represents the availability of 3D structure of the protein.
Fig 5.
The blue rectangle represents the gene and the grey line depicts interaction between a pair of hub genes.
Fig 6.
These high vs. low gene expression curves represent overall survival in breast cancer patients for each of the hub genes identified.
Fig 7.
Functional enrichment re-analysis of hub genes.
A- KEGG pathway enrichment B- Transcription factor enrichment analysis. The most significant results are presented from top to bottom.
Fig 8.
Venn diagram analysis for diabetes and breast cancer (D+BC) comorbid samples with T2DM -adipose tissue and breast adenocarcinoma (BC) samples.
The yellow circle represents DEGs obtained from DEG analysis on T2DM samples, pink circle represents DEGs from BC samples, and sea green circle depict DEGs for D+BC samples, similarly. A- The intersection represents DEGs common to D+BC, T2DM and BC series. B- The intersection represents DEGs common to D+BC and T2DM diseased conditions. C- The intersection represents DEGs common D+BC and BC diseased states.
Table 4.
The DEGs common to the three diseased states in three combinations are listed. The expression of each of the DEGs in diseased state is also indicated. DEGs: differentially expressed genes; T2DM: type 2 diabetes mellitus, BC: breast adenocarcinoma, D+BC: diabetes and breast cancer comorbid state.
Fig 9.
Pathway enrichment and survival analyses.
A-C The most significant KEGG pathway results are presented from top to bottom for A- All three series, B- D+BC and T2DM series C- D+BC and BC series. D- Kaplan-Meier Plot for SIK1 gene. These high vs. low gene expression curves represent overall survival in breast cancer patients for the key gene identified.
Table 5.
Disease specific molecular expression signature patterns.
Peach color indicates up-regulation whereas teal depicts down-regulation. Grey-no differential expression. Darker color intensity significance statistical significance. DEGs: differentially expressed genes; T2DM: type 2 diabetes mellitus, BC: breast adenocarcinoma, D+BC: diabetes and breast cancer comorbid state.
Fig 10.
Schematic model for SIK1 mediated T2DM-BC crosstalk leading to comorbidity.
The figure highlights the two way relationship between T2DM and BC resulting in T2DM induced BC and BC induced T2DM phenotypes. For either direction, the molecular mechanisms underlying SIK1 expression regulated crosstalk are depicted, predicting possible routes to comorbidity.