Table 4.
Analysis of upstream regulators of interactome networks generated from protein changes between Stages I (SI) and II (SII) in either responders or non-responders to ACI were identified using Ingenuity Pathway Analysis software
| Upstream regulators | Activation z score (SII v SI) | p value of overlap | Target molecules in dataset | |
|---|---|---|---|---|
| Non-responders | ||||
| TGFB1 | –1.595 | 9.46E–10 | APOB,APOC2,APOE,CD44,COL1A1,COL1A2,COL5A1,COMP,CSPG4,CTSD,ECM1,FETUB,FN1,FTL,GSN,HINT1,HSPG2,HTRA1,IGFBP6,LCAT,MYLK,PCOLCE2,PDXK,POSTN,RAP1A,S100A4,TGFBI | |
| DYSF | NP | 2.01E–09 | CFD,FN1,FTL,LCP1,LYZ,PROS1,S100-A13,S100A4 | |
| MYC | 3.046 | 2.20E–09 | ALDOA,ANXA5,CCT3,CD44,COL1A1,COL1A2,COL5A1,CSPG4,CTSD,ECM1,FN1,HSPA9,LYZ,NCL,NUCB1,NUDC,PAM,PTN,RPL22,RPL30,TF | |
| COL9A1 | 1.308 | 2.79E–09 | COMP,FN1,HSPG2,TGFBI,THBS4 | |
| Beta-estradiol | 2.271 | 5.01E–09 | ALDOA,APOE,CD44,COL1A1,COL1A2,COMP,CTSD,F7,FN1,GMFB,HSPA2,HSPA8,HSPA9,HTRA1,IGFBP6,LTF,LYZ,MYLK,PAM,PDIA3,QSOX1,RAP1A,RPS13,S100-A13,SLC9A3R1,TF,THBS4 | |
| Lipopolysaccharide | –0.104 | 5.96E–09 | ANXA5,APOB,APOC2,APOE,CD44,CFD,COL1A1,COL1A2,COL5A1,CSPG4,FN1,GSN,HDGFRP3,HMGB2,HSPA8,HTRA1,ITIH2,LBP,LTF,LYZ,PARK7,PCOLCE,PCOLCE2,PDIA3,PLG,TF | |
| Dihydrotestosterone | –1.091 | 1.03E–08 | ALDOA,APOE,CCT3,FN1,FTL,GSN,HINT1,LYZ,MYLK,NUCB1,PAM,POSTN,PROS1,RPL30,TF | |
| HRAS | 0.623 | 2.52E–08 | CD44,COL1A1,COL1A2,ERP29,FN1,GSN,HSPA8,HTRA1,LYZ,MYH10,PDIA5,PLTP,POSTN,RPL30,S100A4 | |
| KRAS | 2.226 | 3.99E–08 | ALDOA,CD44,COL1A1,FN1,GBA,GSN,MYLK,PCOLCE,PDIA3,PSMA7,RNASE4,S100A4 | |
| SMARCB1 | –1.195 | 4.82E–08 | APOC4,CD44,COL1A1,COL1A2,GSN,LBP,POSTN,PTN,RAB14 | |
| Responders | ||||
| CEBPB | –1.067 | 2.03E–07 | APOB,CFD,COL1A1,COL1A2,F7,HSPA8,PLG | |
| FLI1 | NP | 3.82E–07 | COL1A1,COL1A2,HSPA8,PF4 | |
| S-adenosylhomocysteine | NP | 1.21E–06 | COL1A1,COL1A2 | |
| SCX | NP | 1.65E–06 | COL1A1,COMP,POSTN | |
| Tgf beta (group) | –1.454 | 5.16E–06 | COL1A1,COL1A2,LCAT,POSTN,TGFBI | |
| ENTPD5 | NP | 1.21E–05 | COL1A1,COL1A2 | |
| MKX | NP | 1.21E–05 | COL1A1,COL1A2 | |
| GATA4 | NP | 2.86E–05 | COL1A1,COL1A2,POSTN,TGFBI | |
| Nilotinib | NP | 3.39E–05 | COL1A1,COL1A2 | |
| TBX5 | NP | 5.50E–05 | COL1A1,COL1A2,POSTN | |
The 10 upstream regulators with the lowest p values are demonstrated for both responders and non-responders. The p value of overlap is calculated based on the overlap between protein changes within the dataset with known targets of the transcriptional regulator, calculated using a Fisher’s exact test. The activation z score can be used to infer likely activation states of the upstream regulators based on the direction of protein abundance change in the dataset, i.e. a negative activation z score indicates that the upstream regulator is downregulated at Stage II compared to stage I, thus eliciting the specific directions of protein changes of the target molecules at Stage II compared to Stage I of ACI. NP indicates no prediction of activation status could be generated by the software