Gene regulatory network construction identified NFYA as a diffuse subtype-specific prognostic factor in gastric cancer

摘要: Lauren classification is a pathology-based gastric cancer (GC) subtyping system, which widely used in the clinical treatment of patients with GC. However, genome- scale molecular characteristics to distinguish between diffuse (DF) and intestinal (IT) GC remain incompletely characterized, particularly at transcriptional regulatory level. In present study, gene networks were constructed using Passing Attributes Networks for Data Assimilation (PANDA) algorithm DF, IT mixed The results indicated that >85% transcription factor (TF)-target edges shared among all three subtypes. TF enrichment analysis, 13 TFs, including nuclear Y subunit α (NFYA) forkhead box L1, activated DF GC, whereas 8 RELA proto-oncogene T-cell leukemia homeobox 1 (TLX1), Out these identified NFYA [Hazard ratio (HR) (95% confidence interval, CI)=0.560 (0.349, 0.900), P=0.017] sex determining region [HR CI)=0.603 (0.375, 0.969), P=0.037] as independent prognostic factors but not TLX1 CI)=0.547 (0.321, 0.9325), P=0.027] was an Verification cellular level also performed; interference expression small interfering RNA MGC803 cells (DF GC-derived cells) markedly inhibited cell growth colony formation. Similar effects detected SGC-7901 (IT cells), lesser extent. conclusion, differed distinct subtypes, same TFs had different biological effects. Specifically, subtype- specific