title: Nestinservers as a promising prognostic biomarker in non-small cell lung cancer.
abstract: Lung cancer is currently the leading cause of cancer-related death worldwide and it is important to identify the predictive and/or prognostic markers for the cancer.Nestin, a proliferative and multipotent biomarker has been reported to be associated with prognosis in non-small cell lung cancer (NSCLC) in a few studies. In the present study, we retrospectively recruited 153 patients with NSCLC.Nestinprotein expression in tumor samples was determined by immunohistochemistry staining.Nestinexpression was related with tumor differentiation (P=0.036), lymphatic metastasis (N stage, P=0.011), and p-TNM stage (P=0.013), while there was no significant association betweenNestinexpression level and age, smoking habits, gender, histologic type, and T stage.Nestinwas an independent prognostic factor for overall survival in NSCLC with an adjusted hazard ratio of 2.701 (95% CI, 1.616-4.513, P<0.001) after controlling the confounding factors. Then we determined the effects ofNestinon cell proliferation, colony formation, invasion, and apoptosis by knockout ofNestinwith a new developed method, CRISPR/Cas9 mediated genome editing. It was observed that knockout ofNestincaused enhancement of cancer cell apoptosis and inhibition of cell proliferation, colony formation, and invasion in A549 and H1299 cell lines. Furthermore, we examined the expression of epithelial-mesenchymal transition (EMT) related biomarkers such as E-cadherin and Vimentin inNestin-depleted lung cancer cells and knockout ofNestinwas found to inhibit EMT, suggesting the involvement ofNestinmediated EMT signaling in lung cancer. The finding above demonstrated thatNestinmight serve as a prognostic factor and therapeutic target in NSCLCs.
authors.affiliation: Department of Imaging, Shandong Medical College Jinan 250002, Shandong, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Shandong Medical College Jinan 250002, Shandong, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiac Surgery, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, Shandong, China.
authors.forename: Qingbao
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medical Science Jinan 250117, Shandong, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pathology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medical Science Jinan 250117, Shandong, China.
authors.forename: Dianbin
authors.initials: D
authors.lastname: Mu
authors.affiliation: Department of Imaging, Shandong Medical College Jinan 250002, Shandong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Imaging, Shandong Medical College Jinan 250002, Shandong, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medical Science Jinan 250117, Shandong, China.
authors.forename: Xiangjiao
authors.initials: X
authors.lastname: Meng
keywords: Nestin; invasion; non-small cell lung cancer; prognosis; proliferation