Design principles for cancer therapy guided by changes in complexity of protein-protein interaction networks

Biology Direct

Table 2 Betti number analysis and its implication for multiple protein targeting. The data for the 5-year survival was again derived from Surveillance, Epidemiology and End Results Database (SEER), the nominal Betti number was calculated using JPLEX, and represents the Betti number for the full cancer network, and the Best Betti represents the lowest Betti number achieved by removal of a protein from the specific cancer protein-protein interaction (PPI) network. Through sequential removal of protein pairs across the entire PPI network of each cancer, we were able to identify combinations of protein pairs exhibiting most effect on the PPI network. Shown are the node combinations which produce the most reduction in network complexity as measured by the “Best Betti, double node elimination”, each paired node elimination results in equivalent drop in Betti, e.g. HRAS-FLT3 and HRAS-NRAS both have Best Betti of 83 in AML

	AML	Bladder	CML	Colorectal	Endometrial	Glioma	NSCL	Pancreatic	Renal	SCL	Thyroid
5 years Survival [%]	23.6	78.1	55.2	63.6	68.6	33.4	18	5.5	69.5	6.2	97.2
Nominal Betti	107	20	114	51	45	128	50	38	51	149	24
Best Betti [single node elimination]	95	15	101	41	35	109	37	29	34	131	17
Best Betti [double node elimination]	83	11	88	31	26	90	29	21	26	113	10
Paired node elimination		HRAS – MAPK3								ITGA2 – ITGA3
		ARAF – MAPK3								ITGA2 – ITGA6
		RAF1 – MAPK3								ITGA3 – ITGA6
	HRAS – FLT3	NRAS – MAPK3								ITGA2 – ITGA2B
	HRAS – NRAS	HRAS – MAPK1	AKT1 – AKT2	AKT1 – AKT2		NRAS – HRAS				ITGA3 – ITGA2B	HRAS – NRAS
	FLT3 – NRAS	ARAK – MAPK1	AKT1 – AKT3	AKT1 – AKT3	ILK – PDPK1	NRAS – KRAS	EGFR – KRAS	NFKB1 – KRAS	HIF1A – GAB1	ITGA6 – ITGA2B	HRAS – KRAS
	HRAS – KRAS	RAF1 – MAPK1	AKT2 – AKT3	AKT2 – AKT3		HRAS – KRAS	ERBB2 – KRAS	RELA – KRAS	GAB1 – EPAS1	ITGA2 – ITGB1	NRAS – KRAS
	FLT3 – KRAS	NRAS – MAPK1								ITGA3 – ITGB1
	NRAS – KRAS	MAPK3 – KRAS								ITGA6 – ITGB1
		MAPK1 – KRAS								ITGA2B – ITGB1
		MAPK3 – BRAF								ITGA2 – ITGAV
		MAPK1 - BRAF								ITGA3 - ITGAV

ISSN: 1745-6150