Abstract: Objective To analyze the predictive value of serum prostaglandin E2 (PGE2),central nervous system specific protein (S100β) combined with regional cerebral oxygen saturation (rScO2) for postoperative delirium (POD) in elderly patients with colorectal cancer (CRC) frailty.Methods Totally 203 elderly patients with CRC who underwent surgical treatment in our hospital (January 2025 June 2025) were served as the study subjects.ELISA method was used to detect serum PGE2 and S100β in patients.Pearson method was performed to explore the correlation between serum PGE2,S100β,and rScO2.Multivariate Logistic- regression was performed to analyze the factors affecting the occurrence of POD in elderly patients with CRC frailty.The receiver operating characteristic (ROC) curve was used to analyze the predictive value of the combination of serum PGE2,S100β,and rScO2 for POD in elderly patients with CRC frailty.Results The proportions of patients over 75 years old in the POD group and the non-POD group were 64.29% and 44.90% respectively,the serum PGE2 was (364.28±37.42) pg/ml and (329.76±33.65) pg/ml respectively,S100β was (258.64±26.93) pg/ml and (233.37±23.50) pg/ml respectively,and rScO2 was (57.34±5.22) % and (63.36±6.19) % respectively (P<0.05),there was a statistically significant difference between the two groups (P < 0.05).Serum PGE2 and S100β were negatively correlated with rScO2 (r=-0.365,-0.413,both P<0.05).Age (OR=1.994),PGE2 (OR=2.314),S100β (OR=2.426),and rScO2 (OR=0.498) levels were factors that affected the occurrence of POD in elderly patients with CRC frailty (P<0.05).The AUC values of serum PGE2,S100β,and rScO2 alone in predicting POD in elderly patients with CRC frailty were 0.778,0.786,and 0.790,respectively.The  area under curve （AUC） of the combined prediction of the three was 0.930,and their predictive value was conspicuously higher than that of single prediction (ZcombinationPGE2=4.801,Zcombination-S100β=4.417,Zcombination-rScO2=4.362,all P<0.001).The results of 100 internal Bootstrap validations show that the model has good calibration performance,and the calibration curve closely matches the ideal curve.The Hosmer-Lemeshow test results indicate that the model has good goodness of fit (χ2=13.120，degree of freedom=8，P=0.108).Conclusion The combination of serum PGE2,S100β,and rScO2 has a high predictive value for the occurrence of POD in elderly CRC frailty patients.

Key words: prostaglandin E2, central nervous system specific protein, regional cerebral oxygen saturation, colorectal cancer, elderly frailty, postoperative delirium