High expression level of serpin peptidase inhibitor clade E member 2 is associated with poor prognosis in lung adenocarc
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RESEARCH
High expression level of serpin peptidase inhibitor clade E member 2 is associated with poor prognosis in lung adenocarcinoma Ryota Dokuni1, Tatsuya Nagano1* , Naoe Jimbo2, Hiroki Sato1, Tatsunori Kiriu1, Yuichiro Yasuda1, Masatsugu Yamamoto1, Motoko Tachihara1, Kazuyuki Kobayashi1, Yoshimasa Maniwa3 and Yoshihiro Nishimura1
Abstract Background: Recent studies have revealed that serpin peptidase inhibitor clade E member 2 (SERPINE2) is associated with tumorigenesis. However, SERPINE2 expression and its role in lung adenocarcinomas are still unknown. Methods: The expression levels of SERPINE2 in 74 consecutively resected lung adenocarcinomas were analyzed by using immunostaining. Inhibition of SERPINE2 expression by small interfering RNA (siRNA) was detected by quantitative PCR. Cell number assays and cell apoptosis assays were performed to clarify the cell-autonomous function of SERPINE2 in A549 and PC9 lung cancer cells. Results: The overall survival of patients with high SERPINE2 expression was significantly worse than that of patients with low SERPINE2 expression (P = 0.0172). Multivariate analysis revealed that SERPINE2 expression was an independent factor associated with poor prognosis (P = 0.03237). The interference of SERPINE2 decreased cell number and increased apoptosis in A549 and PC9 cells Conclusion: These results suggest that SERPINE2 can be used as a novel prognostic marker of lung adenocarcinoma. Keywords: Serpin peptidase inhibitor clade E member 2, Lung cancer, Adenocarcinoma Background Serine proteinase inhibitor clade E member 2 (SERPINE2), also known as protease nexin-1 (PN-1), was first identified as a neurite-promoting factor released by cultured glioma cells [1]. In addition to glioma cells, various other cells secrete SERPINE2, including endothelial cells, fibroblasts, macrophages, platelets, smooth muscle cells, chondrocytes, astrocytes, and several types of tumor cells [2–6]. SERPINE2 was proven to be a member of the SERPINE family, which has serine protease activity [1, 7]. *Correspondence: [email protected]‑u.ac.jp 1 Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7‑5‑1 Kusunoki‑cho, Chuo‑ku, Kobe 650‑0017, Japan Full list of author information is available at the end of the article
SERPINE2 is overexpressed in a variety of adenocarcinomas, including breast cancer [3], pancreatic cancer [8], gastric cancer [9], and colorectal cancer [10], and its high expression is correlated with the degree of cancer malignancy. A previous study demonstrated that SERPINE2 is upregulated by oncogenic activation of RAS, BRAF and MEK1 and contributes to pro-neoplastic actions of ERK signaling in intestinal epithelial cells [10]. Therefore, SERPINE2 may be a potential therapeutic target for colorectal cancer treatment [10]. In lung adenocarcinomas in particular, high expression of SERPINE2 has been previously reported [11], but the relationship to prognosis or disease progression has never been reported. In this stu
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