Abstract
Interleukin (IL)-38, a novel member of the IL-1 cytokine family, is homologous to IL-1 receptor antagonist (IL-1Ra) and IL-36Ra, and has been reported to act as an antagonist. IL-38 expression is found in tonsil, placenta, and spleen, and recent studies suggest an association between IL-38 and autoimmune diseases. However, whether IL-38 plays a role in carcinogenesis or cancer growth is unclear. In the present study, we identified increases in IL-38 expression by immunohistochemistry in multiple types of cancer cells. In the examination of 417 surgically resected primary lung adenocarcinomas, Fisher’s exact tests showed significant associations between high IL-38 expression and high tumor grades, an advanced T status, advanced N status, advanced stage, and the presence of pleural and vessel invasions. Survival analyses by the Kaplan-Meier method showed that patients with high expression of IL-38 had significantly shorter disease-free survival and shorter overall survival after surgery than patients with low expression of IL-38 (log-rank test: P = 0.0021 and P = 0.0035, respectively). Moreover, programmed cell death-ligand 1 (PD-L1)-positive cases showed higher expression of IL-38 than PD-L1-negative cases (Wilcoxon rank-sum test: P < 0.0001). In conclusion, IL-38 was expressed in tumor cells of various cancers, and IL-38 expression was associated with poor survival of lung adenocarcinoma patients. IL-38 may affect host immunity or the tumor microenvironment, and contribute to the progression of lung adenocarcinoma.
| Original language | English |
|---|---|
| Article number | e0181598 |
| Journal | PloS one |
| Volume | 12 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2017 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
- General
Cite this
Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma : Possible association with PD-L1 expression. / Takada, Kazuki; Okamoto, Tatsuro; Tominaga, Masaki; Teraishi, Koji; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Toyokawa, Gouji; Shoji, Fumihiro; Okamoto, Masaki; Oda, Yoshinao; Hoshino, Tomoaki; Maehara, Yoshihiko.
In: PloS one, Vol. 12, No. 7, e0181598, 07.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma
T2 - Possible association with PD-L1 expression
AU - Takada, Kazuki
AU - Okamoto, Tatsuro
AU - Tominaga, Masaki
AU - Teraishi, Koji
AU - Akamine, Takaki
AU - Takamori, Shinkichi
AU - Katsura, Masakazu
AU - Toyokawa, Gouji
AU - Shoji, Fumihiro
AU - Okamoto, Masaki
AU - Oda, Yoshinao
AU - Hoshino, Tomoaki
AU - Maehara, Yoshihiko
PY - 2017/7
Y1 - 2017/7
N2 - Interleukin (IL)-38, a novel member of the IL-1 cytokine family, is homologous to IL-1 receptor antagonist (IL-1Ra) and IL-36Ra, and has been reported to act as an antagonist. IL-38 expression is found in tonsil, placenta, and spleen, and recent studies suggest an association between IL-38 and autoimmune diseases. However, whether IL-38 plays a role in carcinogenesis or cancer growth is unclear. In the present study, we identified increases in IL-38 expression by immunohistochemistry in multiple types of cancer cells. In the examination of 417 surgically resected primary lung adenocarcinomas, Fisher’s exact tests showed significant associations between high IL-38 expression and high tumor grades, an advanced T status, advanced N status, advanced stage, and the presence of pleural and vessel invasions. Survival analyses by the Kaplan-Meier method showed that patients with high expression of IL-38 had significantly shorter disease-free survival and shorter overall survival after surgery than patients with low expression of IL-38 (log-rank test: P = 0.0021 and P = 0.0035, respectively). Moreover, programmed cell death-ligand 1 (PD-L1)-positive cases showed higher expression of IL-38 than PD-L1-negative cases (Wilcoxon rank-sum test: P < 0.0001). In conclusion, IL-38 was expressed in tumor cells of various cancers, and IL-38 expression was associated with poor survival of lung adenocarcinoma patients. IL-38 may affect host immunity or the tumor microenvironment, and contribute to the progression of lung adenocarcinoma.
AB - Interleukin (IL)-38, a novel member of the IL-1 cytokine family, is homologous to IL-1 receptor antagonist (IL-1Ra) and IL-36Ra, and has been reported to act as an antagonist. IL-38 expression is found in tonsil, placenta, and spleen, and recent studies suggest an association between IL-38 and autoimmune diseases. However, whether IL-38 plays a role in carcinogenesis or cancer growth is unclear. In the present study, we identified increases in IL-38 expression by immunohistochemistry in multiple types of cancer cells. In the examination of 417 surgically resected primary lung adenocarcinomas, Fisher’s exact tests showed significant associations between high IL-38 expression and high tumor grades, an advanced T status, advanced N status, advanced stage, and the presence of pleural and vessel invasions. Survival analyses by the Kaplan-Meier method showed that patients with high expression of IL-38 had significantly shorter disease-free survival and shorter overall survival after surgery than patients with low expression of IL-38 (log-rank test: P = 0.0021 and P = 0.0035, respectively). Moreover, programmed cell death-ligand 1 (PD-L1)-positive cases showed higher expression of IL-38 than PD-L1-negative cases (Wilcoxon rank-sum test: P < 0.0001). In conclusion, IL-38 was expressed in tumor cells of various cancers, and IL-38 expression was associated with poor survival of lung adenocarcinoma patients. IL-38 may affect host immunity or the tumor microenvironment, and contribute to the progression of lung adenocarcinoma.
UR - http://www.scopus.com/inward/record.url?scp=85024889153&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85024889153&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0181598
DO - 10.1371/journal.pone.0181598
M3 - Article
C2 - 28727766
AN - SCOPUS:85024889153
VL - 12
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 7
M1 - e0181598
ER -