Interleukin-38 in colorectal cancer: a potential role in precision medicine

Colorectal cancer (CRC) is a leading cause of cancer-related death, partly due to a lack of reliable biomarkers for early diagnosis. To improve the outcome of CRC, it is critical to provide diagnosis at an early stage using promising sensitive/specific marker(s). Using immunohistochemistry and histopathology, IL-38 expression was determined in tissue arrays of CRC with different TNM status and depth of tumour invasion. Data were compared to IL-38 in adjacent non-cancer tissue and correlated with demographic information, including survival. A substantial reduction of IL-38 was detected in the CRC tissue compared to adjacent non-cancer colonic tissue. IL-38 correlated with the extent of tumour differentiation (P < 0.0001); CRC location in the left side of the colon (P < 0.05), and smaller tumour size (≤ 5 cm; P < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated both high specificity and high sensitivity of IL-38 for the diagnosis of CRC [area under the curve (AUC) = 0.89)]. By sub-group analysis, AUC of IL-38 for the diagnosis of CRC was higher in poorly differentiated, right-sided CRC or tumour size > 5 cm (all AUC > 0.9). Significantly, longer survival was observed for the IL-38^high versus the IL-38^low groups in CRC patients (P = 0.04). Survival was also longer for IL-38^high patients with lymph node metastasis (P = 0.01) and TNM stage III-IV (P = 0.02). Multivariate analysis demonstrated that IL-38 (P = 0.05) and tumour invasion depth (P = 0.04) were independent factors for survival. High IL38 in CRC is an independent prognostic factor for the longer survival of CRC patients. IL-38 signalling may constitute a therapeutic target in CRC.