Table 3.

Predicted upstream regulators affected in GOT1 tumors after ¹⁷⁷Lu-octreotate therapy with priming

	Upstream regulator	z	p	Targets from transcriptional data
1 day
	GDF15	–	6.1 × 10−6	↑CDKN1A, ↑GDF15
	PPP5C	–	1.8 × 10−5	↑CDKN1A, ↑SGK
	SATB1	0.11	7.8 × 10−5	↑CDKN1A, ↑F5, ↑FAM129A, ↑SGK
	RNF2	–	1.3 × 10−4	↑CDKN1A, ↑GDF15
	FH	–	2.2 × 10−4	↑APOD, ↑CDKN1A
3 days
►	p53	3.3	6.0 × 10−14	↑ACTA2, ↑APOE, ↑BAX, ↑CCND3, ↑CDKN1A, ↓CTGF, ↑DDB2, ↑DDIT3, ↓FDFT1, ↑GADD45A, ↑GDF15, ↑NINJ1, ↓PBK, ↑PHLDA3, ↑SPATA18, ↑TIGAR, ↑TNFRSF10B, ↑VCAN
►	ANXA2	−2.0	8.1 × 10−9	↑BAX, ↑CDKN1A, ↑GADD45A, ↑TNFRSF10B, ↑ZMAT3
	MYC	−0.32	2.0 × 10−8	↑BAX, ↑CCND3, ↑CDKN1A, ↑DDB2, ↑DDIT3, ↓EXOSC8, ↑GADD45A, ↑HSPH1, ↑TNFRSF10B
	PPARGC1A	0.32	8.3 × 10−8	↑BAX, ↑CDKN1A, ↓INSIG1, ↓LDLR, ↑TIGAR
►	KDM5B	2.6	2.0 × 10−5	↑DDIT3, ↓DLGAP5, ↑GADD45A, ↓INSIG1, ↓PBK
7 days
	PPARG	0.17	9.8 × 10−8	↑ACTA2, ↑CDH1, ↑CDKN1A, ↑CTSL, ↓INSIG1, ↓PDK4
►	PARP1	−2.0	3.7 × 10−7	↑CDH1, ↓PEG10, ↓TMSB15A, ↑TNFRSF10B
	p53	1.9	1.0 × 10−6	↑ACTA2, ↑APOE, ↑CDH1, ↑CDKN1A, ↑F5, ↓FDFT1, ↑GDF15, ↑NINJ1, ↓PEG10, ↑PHLDA3, ↓TMSB15A, ↑TNFRSF10B
	SKI	–	1.1 × 10−6	↑ACTA2, ↑CDH1, ↑CDKN1A
	GDF15	–	1.5 × 10−5	↑CDKN1A, ↑GDF15
41 days
►	LIN28B	–	4.5 × 10−5	↓BCL11A, ↓SOX2
	ID1	–	1.9 × 10−4	↓EGR1, ↓SOX2
►	CDX2	–	1.1 × 10−3	↓NR2F2, ↓SOX2
	SHP	–	1.3 × 10−3	↓EGR1
	mir-140	–	1.3 × 10−3	↓SOX2

Significantly affected upstream regulators identified with IPA (Fisher’s exact test, p < 0.05), ranked according to the lowest p value, for each time point. z scores indicate activation state of the upstream regulator; z > 2 indicates activation, and z < −2 indicates inhibition. Up and down arrows indicate upregulated and downregulated genes in tumor samples from treated animals compared with controls, respectively. ► indicates the upstream regulator was not affected in animals treated with 15 MBq single administration of ¹⁷⁷Lu-octreotate (from GEO accession GSE80024)