title: USP7 overexpression predicts a poor prognosis in lung squamous cell carcinoma and large cell carcinoma.
abstract: In non-small cell lung cancer (NSCLC), both USP7 expression and p53 gene status were reported to be an indicator of poor prognosis in adenocarcinoma patients; however, its roles and mechanisms in lung squamous cell carcinoma and large cell carcinoma need to be clarified. The USP7 expression was examined in NSCLC tumors (excluding adenocarcinoma), their corresponding non-tumorous tissues, and NSCLC cells. Then, the prognostic role of USP7 was analyzed in 110 NSCLC samples (excluding the adenocarcinoma). Finally, the roles and mechanisms of USP7 in the proliferation, metastasis, and invasion of a NSCLC cell were assessed using a specific vshRNA. The USP7 expression was higher in NSCLC tissues compared to non-tumorous samples, accordingly, the high level of USP7 was detected in NSCLC cell lines compared with HBE cell. After the USP7 downregulation, the H460 cells exhibited decreased metastasis/invasion in vitro and in vivo. The preliminary mechanism study indicated overexpression of USP7 might regulate the p53-MDM2 pathway by inducing the MDM2 de-ubiquitination and subsequent stabilization, which resulted in the upregulation of the Bad phosphorylation. Additionally, we also found that USP7 might induce cell epithelial-mesenchymal transition to enhance the cell invasive ability. Clinically, USP7 overexpression significantly correlated with malignant phenotype. Furthermore, the 5-year overall survival in patients with USP7(low) was higher than that of USP7(high). Multivariate analysis showed USP7 overexpression was an independent prognostic marker for these cancers. USP7 overexpression may regulate the survival and invasive properties of squamous cell carcinoma and large cell carcinoma cells, and may serve as a molecular target.
authors.affiliation: Department of Thoracic Surgery, The Affiliated Zhongshan Hospital of Fudan University, 200032, Shanghai, People's Republic of China.
authors.forename: Guang-Yin
authors.initials: GY
authors.lastname: Zhao
authors.forename: Zong-Wu
authors.initials: ZW
authors.lastname: Lin
authors.forename: Chun-Lai
authors.initials: CL
authors.lastname: Lu
authors.forename: Jie
authors.initials: J
authors.lastname: Gu
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Yuan
authors.forename: Feng-Kai
authors.initials: FK
authors.lastname: Xu
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Liu
authors.forename: Di
authors.initials: D
authors.lastname: Ge
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Ding
mesh_terms: D000818:Animals; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000096:biosynthesis* / Q000235:genetics; D000076084:Ubiquitin-Specific Peptidase 7; D015854:Up-Regulation
chemical_list: D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7