Table 2.

Predicted upstream regulators in GOT1 tumors after sonidegib, ¹⁷⁷Lu-octreotate, or a combination of both treatments

Upstream Regulator	Molecule Type		p-value:		Targets from data
		Sonidegib	177Lu-octreotate	Combination
A
SUZ12	Enzyme	2.0·10−2	4.6·10−3	1.3·10−4	UP: CDKN2A, HSD17B11, LITAF DOWN: CXCR7, KCNA1, RBMS1
CTBP1	Enzyme	2.4·10−3	3.9·10−2	1.3·10−2	UP: CDKN1A DOWN: CXCR7
PRKCA	Kinase	1.2·10−2	1.9·10−2	2.5·10−3	DOWN: BCL11A, EGR1, ETS1, HSPA1B, PVR
HIC1	Transcription regulator	1.6·10−2	2.9·10−2	3.3·10−2	UP: CDO1 DOWN: CXCR7, ID4, KCNJ6
miR-292b-5p	Mature microRNA	1.1·10−3	1.8·10−2	-	DOWN: BCL11A
LIN28B	Other	1.3·10−3	2.2·10−2	-	DOWN: BCL11A
CHD4	Enzyme	2.7·10−3	4.4·10−2	-	DOWN: BCL11A
EZH2	Transcription regulator	2.4·10−2	8.1·10−3	-	DOWN: CXCR7, KCNA1, NFKBIA
MAPK1	Kinase	4.2·10−2	3.5·10−2	-	UP: HBA2 DOWN: BCL11A, CTNNA2
Histone h3	Group	3.9·10−2	-	2.1·10−4	UP: BTG3, CDKN1A, CDKN2A, ENO3, PCNA, RGS10, STOM DOWN: CXCR7, NFKBIA, SOD2
Ctbp	Group	3.2·10−3	-	2.3·10−2	UP: CDKN2A DOWN: CXCR7
ETS1	Transcription regulator	1.7·10−2	-	4.2·10−2	DOWN: BCL11A, CTGF, HSPA1B, PVR
B
Upstream Regulator	Molecule Type	z	p-value	Targets from data
INS	Other	−2.1	2.6·10−4	UP: CBS, LPL DOWN: EGR1, OGT, SREBF1
FSH	Complex	2.2	7.5·10−3	UP: DLX5, GNAS, PMAIP1, RGS16, SC4MOL DOWN: BCL11A, DUSP3, FILIP1L, FLNC, ILK, ITGA3, TPM2
Lh	Complex	2.2	2.4·10−2	UP: GNAS, PMAIP1, RGS16, SC4MOL DOWN: DUSP3, FLNC, ILK, ITGA3, TPM2

A) Upstream regulators with statistically significant p-values (p < 0.05) in at least two treatment groups. B) Upstream regulators with activation |z-score| > 2, identified in tumor samples treated with a combination of sonidegib and ¹⁷⁷Lu-octreotate. No upstream regulators with |z-score| > 2 were found in either monotherapy group. z > 2 indicates activation, z < −2 indicates inhibition. UP and DOWN indicate up- and downregulation, respectively