title: NQO1 protein expression predicts poor prognosis of non-small cell lung cancers.
abstract: BACKGROUND
  High-level expression of
  quinoneoxidoreductase 1 (NQO1) has been correlated with many types of human cancers, suggesting that NQO1 plays important roles in tumor occurrence and progression. This study attempted to explore the role of NQO1 in tumor progression and prognostic evaluation of non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Total 164 tissue samples, including 150 NSCLC paired with the adjacent non-tumor tissues and 14 normal lung tissues, were picked-up for immunohistochemical (IHC) staining of the NQO1 protein, and immunofluorescence (IF) staining was also performed to detect the subcellular localization of the NQO1 protein in A549 human lung cancer cells. The correlation between NQO1 expression and clinicopathological characteristics were evaluated by Chi-square test and Fisher's exact tests. The disease-free survival (DFS) and overall survival (OS) rates of NSCLC patients were calculated by the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model.
  
  
  RESULTS
  The NQO1 protein showed a mainly cytoplasmic staining pattern in lung cancer cells, including adenocarcinoma and squamous cell carcinoma (SCC). Both positive rate and strongly positive rate of NQO1 protein expression were significantly higher in NSCLC (59.3% and 28.0%) than that in adjacent non tumor (8.0% and 1.3%) and normal lung tissues (0%). The positive rate of NQO1 was related with clinical stage and lymph node metastasis, and the strongly positive rate of NQO1 protein was significantly correlated with tumor size, poor differentiation, advanced clinical stage and lymph node metastasis in NSCLC. Additionally, survival analyses showed that the patients with NQO1 positive expression had lower OS rates compared with those with NQO1 negative expression in the groups of T1-2, T3-4, without LN metastasis and stage I-II of NSCLC, respectively; however, in the groups of patients with LN metastasis or III-IV stages, OS rate was not correlated with NQO1 expression status. Moreover, multivariate analysis suggested that NQO1 emerged as a significant independent prognostic factor along with tumor size, differentiation, lymph node metastasis and clinical stage in patients with NSCLC.
  
  
  CONCLUSIONS
  NQO1 is upregulated in NSCLC, and it may be a useful poor prognostic biomarker and a potential therapeutic target for patients with NSCLC.
authors.affiliation: Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, 133002, China. lizzy-329@hotmail.com.
authors.forename: Zhenling
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of TCM, Jilin Cancer Hospital, Changchun, 130012, China. zhangyuejlcc@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, 133002, China. jintf@ybu.edu.cn.
authors.forename: Tiefeng
authors.initials: T
authors.lastname: Jin
authors.affiliation: Department of Anatomy and Histology and Embryology, Yanbian University Medical College, Yanji, 133002, China. 164155897@qq.com.
authors.forename: Jiguang
authors.initials: J
authors.lastname: Men
authors.affiliation: Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, 133002, China. zhlin720@ybu.edu.cn.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Anatomy and Histology and Embryology, Yanbian University Medical College, Yanji, 133002, China. 793340660@qq.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Qi
authors.affiliation: Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, 133002, China. yspiao@ybu.edu.cn.|Department of Pathophysiology, Yanbian University Medical College, Yanji, 133002, China. yspiao@ybu.edu.cn.
authors.forename: Yingshi
authors.initials: Y
authors.lastname: Piao
authors.affiliation: Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, 133002, China. guanghyan@hotmail.com.|Department of Anatomy and Histology and Embryology, Yanbian University Medical College, Yanji, 133002, China. guanghyan@hotmail.com.
authors.forename: Guanghai
authors.initials: G
authors.lastname: Yan
mesh_terms: D000328:Adult; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human