Table 2.

Predicted upstream transcriptional regulators and functional modules induced by TRE serum

Functional module	Transcriptional regulators	Direction	Interpretation
Integrated stress response (ISR)/metabolic adaptation	ATF4, FOXO1, FOXO3, KLF15	↑ Activated	Nutrient stress adaptation, amino acid sensing, metabolic reprogramming
Interferon/innate immune signaling	IRF1, IRF2, IRF9, STAT1, STAT2	↑ Activated	Innate immune-like signaling, consistent with stress-induced transcriptional programs
NF-κB-associated signaling	NFKB1, REL, RELA	↑ Activated	Stress-responsive transcriptional regulation; likely reflects adaptive signaling rather than classical inflammatory activation
Antigen presentation (MHC II regulation)	CIITA, RFXANK, RFX5	↑ Activated	Enhanced immune surveillance/antigen processing pathways
Lipid and cholesterol metabolism	SREBF1, SREBF2	↓ Inhibited	Suppression of anabolic lipid biosynthesis consistent with mTORC1 inhibition
Endothelial homeostasis/quiescence	HOPX	↓ Inhibited	Shift from quiescent toward a more responsive/adaptive endothelial state
Genomic stability/stress response	BRCA1, HMGB2, ABL1	↑ Activated	DNA damage response and cellular stress adaptation mechanisms