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IL-36 s in the colorectal cancer: is interleukin 36 good or bad for the development of colorectal cancer?

  • Chen, Feier1, 2
  • Qu, Meng3
  • Zhang, Feng1
  • Tan, Zhenyu1
  • Xia, Qinghua4
  • Hambly, Brett D.1, 2
  • Bao, Shisan1, 2
  • Tao, Kun1
  • 1 Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China , Shanghai (China)
  • 2 The University of Sydney, Sydney, Australia , Sydney (Australia)
  • 3 Beihua University School of Medicine, Jilin, China , Jilin (China)
  • 4 Centre for Disease Control and Prevention of Changning District, Shanghai, China , Shanghai (China)
Published Article
BMC Cancer
Springer (Biomed Central Ltd.)
Publication Date
Feb 03, 2020
DOI: 10.1186/s12885-020-6587-z
Springer Nature


Background and aimsColorectal 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.MethodsCRC 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.ResultsA 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-36αhigh and IL-36αlow (P = 0.003) or IL-36γhigh and IL-36γlow (P = 0.03). Survival curves varied significantly when further stratification into sub-groups, 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 sub-groups with a combination of IL-36αhigh plus IL-36βhigh, or IL-36αhigh plus IL-36γlow exhibited the longest survival time among CRC patients. In contrast, the sub-groups of IL-36αlow plus IL-36βhigh or IL-36αlow plus IL-36γhigh had the shortest overall survival. Using the log-rank test, IL-36αhigh 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-36γlow 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.ConclusionIL-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.

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