Gene expression profile analysis unravelled the systems level association of renal cell carcinoma with diabetic nephropathy and Matrix�metalloproteinase-9 as a potential therapeutic target.

Type 2 diabetes (T2D) and cancer share many common risk factors. However, the potential biological
link that connects the two at the molecular level is still unclear. The experimental evidence suggests
that several genes and their pathways may be involved in developing cancerous conditions associated
with diabetes. In this study, we identified the protein-protein interaction (PPI) networks and the hub
protein(s) that interlink T2D and cancer using genome-scale differential gene expression profiles.
Further, the PPI network of AMP-activated protein kinase (AMPK) in cancer was analyzed to explore
novel insights into the molecular association between the two conditions. The densely connected
regions were analyzed by constructing the backbone and subnetworks with key nodes and shortest
pathways, respectively. The PPI network studies identified Matrix-metalloproteinase-9 (MMP-9) as a
hub protein playing a vital role in glomerulonephritis tubular diseases and some genetic kidney dis�eases. MMP-9 was also associated with different growth factors, like tumor necrosis factor (TNF-a),
transforming growth factor 1 (TGF-1), and pathways like chemokine signaling, NOD-like receptor sig�naling, etc. Further, the molecular docking and molecular dynamic simulation studies supported the
druggability of MMP-9, suggesting it as a potential therapeutic target in treating renal cell carcinoma
linked with diabetic kidney disease.