Gene Expression Profiling for Postoperative Cognitive Dysfunction (POCD) Among High Risk Coronary Artery Bypass Graft (CABG) Patients

Postoperative cognitive dysfunction (POCD) is the undesirable complication following
surgery that significantly impacts patients’ quality of life. The outcome of POCD is
characterized by mental disorders, anxiety, personality changes and impaired memory. This
study aimed to identify the differentially expressed genes (DEGs) in high-risk CABG
patients with POCD and the level of the protein biomarker that correlates with the
expressed gene. Forty-six patients scheduled for high-risk CABG procedures were selected
based on inclusion and exclusion criteria. Cognitive assessments were done one day before
and seven days after surgery to classify POCD. For DEGs analysis using microarray,
ribonucleic acid (RNA) samples were collected from patients’ blood one day preoperative
and 3 days postoperatively. A total of 16 samples from the 46 patients were selected for
microarray analysis. Further, an enzyme-linked immunosorbent assay (ELISA) was
conducted to determine the level of protein biomarkers related to the DEGs. Independent
T-test and paired T-test were performed to compare the differences between groups. Based
on pre and postoperative analysis of POCD patients, the findings revealed 5 differentially
expressed genes. The downregulated genes were KIR3DL2, KIR2DS3, and KIR2DS2,
which are involved in immunoregulatory responses, and LIM2, a gene involved in
cataractogenesis. Whilst the upregulated gene was ERFE, that is involved in iron
metabolisms. For postoperative analysis of POCD and non-POCD patients, one gene was
downregulated, which is BTNL3, that involved is in immunoregulation. A significantly
higher concentration of erythroferrone protein, ERFE, was found in POCD patients’ plasma
than in non-POCD patients (p<0.05). Receiver Operating Characteristic (ROC) curve was
generated and revealed that ERFE has a moderate performance in predicting POCD with
the threshold set at 0.761 with specificity and sensitivity at 80% and 50% (AUC:0.685,
95% CI: 0.564 to 0.802, p<0.05). In conclusion, immunoregulatory and iron metabolism
genes are potential genes involved in POCD development. ERFE concentration in plasma
may potentially be used as a biomarker for clinicians to predict POCD. This study serves
as a pioneer in understanding POCD at the molecular level.