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. 2017 Mar 13;12(3):e0173331. doi: 10.1371/journal.pone.0173331

Table 3. Summary of predicted dysregulated signaling pathways from KEGG, Reactome and WikiPathway databases that plays a role as compensatory pathway of EGFR/HER2 inhibition in acquired resistance in both SKBR3 and BT474 cell-lines.

Aberrant Pathways in EGFR-TKIs Resistance^k,r,w	% of Direct Pair^{(s,b)^k,r,w}	% of Indirect Pair^{(s,b)^k,r,w}	% of PPI Pair^{(s,b)^k,r,w}	# of Enriched Pair^{(s,b)^k,r,w}	Enrichment q-value^{(s,b)^k,r,w}	Literature References
Compensating Pathways of EGFR/HER2 inhibition
Notch signaling	(40%, 75%)^k	(__, 25%)^k	—	(2, 3)^k	(8.6e-08, 1.7e-12)^k	[48–50]
	(46.15%, 71.43%)^r	(7.69%, 4.76%)^r	—	(5, 7)^r	(5.2e-17, 3.6e-23)^r
	(35%, 70.37%)^w	(__, 7.41%)^w	—	(5, 7)^w	(3.2e-14, 3.2e-20)^w
Wnt signaling	(25%, 50%)^k	(12.5%, 28.57%)^k	—	(6, 8)^k	(3.4e-16, 3.2e-25)^k	[51, 52]
	(21.88%, 66.67%)^r	(3.12%, 3.33%)^r	—	(2, 2)^r	(2.9e-04, 2.7e-04)^r
	(25%, 55.56%)^w	(12.5%, 11.11%)^w	—	(3, 6)^w	(1.7e-19, 2.1e-10)^w
Insulin Receptor/IGF1R signaling	(40%, 70.49%)^k	(13.33%, 9.84%)^k	—	(6, 25)^k	(7.9e-16, 3.1e-72)^k	[3, 10, 46, 47]
	(29.41%, 87.93%)^r	(5.88%, 3.45%)^r	—	(4, 30)^r	(1.3e-11, 6.6e-94)^r
	(35.9%, 80%)^w	(12.82%, 9.33%)^w	(__, 1.33%)^w	(6, 28)^w	(4.1e-13, 2.9e-70)^w
VEGFR signaling	(40%, 81.82%)^k	(__, 4.55%)^k	—	(1, 15)^k	(1.9e-03, 3.6e-54)^k	[3, 55]
FGFR signaling	(32.05%, 71.14%)^r	(8.97%, 6.97%)^r	(__, 0.5%)^r	(18, 72)^r	(7.6e-43, 1.7e-185)^r	[4, 56]
PDGFR signaling	(40.78%, 71.35%)^r	(3.88%, 3.78%)^r	(__, 0.54%)^r	(15, 67)^r	(2.2e-32, 1.9e-171)^r	[21]
Others
Hippo signaling	(41.46%, 72.22%)^k	(12.2%, 11.11%)^k	—	(9, 4)^k	(1.0e-24, 6.7e-12)^k	[59]
TGF-β signaling	(22.22%, 100%)^k	(11.11%, __)^k	—	(4, 1)^k	(1.1e-13, 5.0e-04)^k	[10, 60]
	(50%, 50%)^r	(25%, __)^r	—	(2, 1)^r	(4.4e-07, 7.7e-04)^r
	(54.55%, 30%)^w	(18.18%, 40%)^w	—	(5, 4)^w	(1.1e-16, 1.2e-13)^w

^k KEGG

^r Reactome

^w WikiPathway

^s SKBR3

^b BT474;