title: Contribution of upregulated dipeptidyl peptidase 9 (DPP9) in promoting tumoregenicity, metastasis and the prediction of poor prognosis in non-small cell lung cancer (NSCLC).
abstract: Dipeptidyl peptidase 9 (DPP9) is encoded by DPP9, which belongs to the DPP4 gene family. Proteins encoded by these genes have unique peptidase and extra-enzymatic functions that have been linked to various diseases including cancers. Here, we describe the expression pattern and biological function of DPP9 in non-small-cell lung cancer (NSCLC). The repression of DPP9 expression by small interfering RNA inhibited cell proliferation, migration, and invasion. Moreover, we explored the role of DPP9 in regulating epithelial-mesenchymal transition (EMT). The epithelial markers E-cadherin and MUC1 were significantly increased, while mesenchymal markers vimentin and S100A4 were markedly decreased in DPP9 knockdown cells. The downregulation of DPP9 in the NSCLC cells induced the expression of apoptosis-associated proteins both in vitro and in vivo. We investigated the protein expression levels of DPP9 by tissue microarray immunohistochemical assay (TMA-IHC) (n = 217). Further we found mRNA expression levels of DPP9 in 30 pairs of clinical NSCLC tissues were significantly lower than in the adjacent non-cancerous tissues. Survival analysis showed that the overexpression of DPP9 was a significant independent factor for poor 5-year overall survival in patients with NSCLC (p = 0.003). Taken together, DPP9 expression correlates with poor overall survival in NSCLC.
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pathology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Xumei
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Min
authors.initials: M
authors.lastname: Ge
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors.forename: Songshi
authors.identifier: 0000-0002-1381-5298
authors.initials: S
authors.lastname: Ni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality; D002465:Cell Movement; D049109:Cell Proliferation; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4 / Q000378:metabolism; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D014746:Vimentin / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000071999:S100 Calcium-Binding Protein A4; D014746:Vimentin; C077591:S100A4 protein, human; C471241:DPP9 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
keywords: DPP9; NSCLC; apoptosis; metastasis; prognosis