Abstract
Interleukin (IL)‐37 and neutrophils are considered to be involved in human cancer, but their prognostic significance in colorectal cancer (CRC) has not been elucidated. The aim of this study was to evaluate the prognostic value of IL‐37 expression and neutrophil levels in CRC. We retrospectively analyzed IL‐37 expression, CD66b+ neutrophil levels, and mismatch repair (MMR) status in 337 paraffin‐embedded CRC specimens from the training cohort by immunohistochemistry. Their prognostic values were assessed using Kaplan‐Meier curves and multivariate Cox regression models. Moreover, several risk factors were used to form nomograms to evaluate survival, and the performance of the nomograms was assessed with respect to calibration, discrimination, and clinical usefulness. Further validation was performed in an independent cohort of 245 cases. Low IL‐37 expression and high CD66b+ neutrophil levels were significantly associated with diminished disease‐free survival (DFS) and overall survival (OS), and patients with MMR‐deficient CRC had better clinical outcomes. Furthermore, multivariate Cox analysis identified IL‐37, CD66b+ neutrophils, and MMR status as independent prognostic factors for DFS and OS. Two nomograms integrating the three markers with four clinicopathological risk factors were developed and validated for predicting DFS and OS with good calibration and discrimination (C‐index: training cohort, 0.798 (95% confidence interval:0.764‐0.832) and 0.828 (0.796‐0.860), respectively; validation cohort, 0.739 (0.696‐0.783) and 0.761 (0.715‐0.808), respectively). Decision curve analysis demonstrated that the nomograms were clinically useful. Intratumoral IL‐37, CD66b+ neutrophils, and MMR status were independent prognostic factors for CRC patients. Nomograms incorporating these biomarkers and clinicopathological features could be conveniently used to facilitate the individualized prediction of DFS and OS.
Highlights
Colorectal cancer (CRC) is one of the most common malignancies and accounts for a significant number of cancer- related deaths worldwide.[1]
We investigated the prognostic value of CD66b+ tumor-a ssociated neutrophils (TANs) and MMR status and the interrelationship of IL-3 7, CD66b+TANs, and MMR status
Tissue sections were screened at a low power (100×), and five representative fields were selected at a high power (200×) with Leica DM IRB inverted research microscope (Leica Microsystems, Wetzlar, Germany)
Summary
Colorectal cancer (CRC) is one of the most common malignancies and accounts for a significant number of cancer- related deaths worldwide.[1]. Gao et al[9] found that the intratumoral injection of IL-37 inhibited tumor growth and the antitumor activity of IL-37 was abrogated in mice models. Recent study by Zhao found that IL-3 7 inhibited colon tumor formation in the mice model and sensitized the cancer cell to chemotherapy drugs.[15]. This suggests that IL-37 could play an important role in tumor growth and may be useful for chemotherapy and tumor immunotherapy. Despite this knowledge, the molecular and prognostic functions of IL-37 in CRC are not yet conclusive
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