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. 2018 Mar 2;13(3):e0193428.
doi: 10.1371/journal.pone.0193428. eCollection 2018.

Lower expression level of IL-33 is associated with poor prognosis of pulmonary adenocarcinoma

Affiliations

Lower expression level of IL-33 is associated with poor prognosis of pulmonary adenocarcinoma

Min Yang et al. PLoS One. .

Abstract

Objective: Lung cancer is one of the deadliest malignancies. The immune checkpoint-blockade (ICB) tumor therapy has led to striking improvement of long-term survival for some lung cancer patients. However, the response rate of immunotherapy is still low for lung cancer. Studying the tumor microenvironment (TME) should shed light on improvement of immunotherapy of lung cancer. Interleukin-33 (IL-33), an "alarmin" cytokine, has been implicated in tumor associated immune responses and inflammatory diseases of the lung. The role of IL-33 in lung cancer progression, however, remains elusive. This study is designed to characterize IL-33 expression in lung tumor tissues and establish the clinical significance of IL-33 in non-small cell lung cancer lung cancer (NSCLC).

Materials and methods: Tumor tissue specimens from patients suffering from NSCLC were analyzed for expression of IL-33 protein by immunohistochemistry and expression of IL-33 and ST2 mRNA by RT-quantitative PCR (RT-QPCR). The expression data were analyzed for their association with clinical and pathological parameters of NSCLC. In addition, the association between expression levels of IL-33 mRNA and patient survival was determined using 5 independent expression profiling datasets of human lung cancer.

Results and conclusion: The expression levels of IL-33 and ST2 were significantly down-regulated in both adenocarcinoma and squamous cell carcinoma of the lung when compared to adjacent normal lung tissues. In addition, the level of IL-33 protein was inversely correlated with tumor grade and size. Moreover, analysis of TCGA and GEO lung cancer expression datasets revealed that higher expression levels of IL-33 mRNA were correlated with longer overall survival of patients suffering from adenocarcinoma of the lung. These data indicate that the expression levels of IL-33 are inversely associated with lung cancer progression, consistent with the hypothesis that IL-33 is involved in immune surveillance of NSCLC.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. IL-33 is expressed in normal lung tissue.
Representative images of immunohistochemistry staining analysis of IL-33 (brown) expression in human lung tissues. (A) bronchial epithelial cells, (B) chondrocytes, (C) vascular endothelial cell (D) alveolus and glandular cells.
Fig 2
Fig 2. IL-33 is down-regulated in NSCLC.
Representative immunohistochemistry staining of IL-33 (brown) in tumor (A, C) and adjacent normal (B, D) tissues from adenocarcinoma (A, B) and squamous cell carcinoma (C, D) in NSCLC.
Fig 3
Fig 3. Both IL-33 and ST2 are down-regulated in NSCLC.
Statistical analysis of IL-33 and its receptor ST2 mRNA expression levels in adenocarcinoma (A, C) and squamous cell carcinoma (B, D) tissues as well as their adjacent normal tissues from NSCLC patients. n = 80 and 47 respectively, Mann-Whitney test.
Fig 4
Fig 4. Higher levels of IL-33 mRNA were correlated with prolonged overall survival of adenocarcinoma NSCLC.
Survival analysis of Adenocarcinoma (A) and squamous cell carcinoma (B) with high or low IL-33 expression in NSCLC patients. Data are collected from TCGA. Log-rank test was performed.

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