Background and aims: Colorectal cancer (CRC) is a major killer. Host immunity is important in tumorigenesis. Direct comparison among IL-36α, IL-36β and IL-36γ in the prognosis of CRC is unclear. Methods: CRC tissue arrays were generated from colorectostomy samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, IL-36α, IL-36β and IL-36γ were determined, in comparison to non-cancer tissues. Results: A significant association was observed between colonic IL-36α, IL-36β or IL-36γ and the presence of cancer (with all P < 0.0001). Using ROC curve analysis, specificity and sensitivity of IL-36α, IL-36β or IL-36γ were confirmed, with area under the curve (AUC) values of 0.68, 0.73 and 0.65, respectively. Significant differences in survival were observed between IL-36α high and IL-36α low (P = 0.003) or IL-36γ high and IL-36γ low (P = 0.03). Survival curves varied significantly when further stratification into subgroups , on the basis of combined levels of expression of two isotypes of IL-36 was undertaken. A significant difference was observed when levels of IL-36α and IL-36β were combined (P = 0.01), or a combination of IL-36α plus IL-36γ (P = 0.002). The subgroups with a combination of IL-36α high plus IL-36β high , or IL-36α high plus IL-36γ low exhibited the longest survival time among CRC patients. In contrast, the subgroups of IL-36α low plus IL-36β high or IL-36α low plus IL-36γ high had the shortest overall survival. Using the log-rank test, IL-36α high expression significantly improved survival in patients with an invasion depth of T4 (P < 0.0001), lymph node metastasis (P = 0.04), TNM III-IV (P = 0.03) or with a right-sided colon tumour (P = 0.02). Similarly, IL-36γ low expression was significantly associated with improved survival in patients with no lymph node metastasis (P = 0.008), TNM I-II (P = 0.03) or with a left-sided colon tumour (P = 0.05). Multivariate analysis demonstrated that among IL-36α, IL-36β and IL-36γ, only IL-36α (HR, 0.37; 95% CI, 0.16-0.87; P = 0.02) was an independent factor in survival, using Cox proportional hazards regression analysis. Conclusion: IL-36α or IL-36γ are reliable biomarkers in predicting the prognosis of CRC during the later or early stages of the disease, respectively. Combining IL-36α plus IL-36γ appears to more accurately predict the postoperative prognosis of CRC patients. Our data may be useful in the management of CRC.
