title: Clinicopathological significance of orphan nuclear receptor Nurr1 expression in gastric cancer.
abstract: BACKGROUND
  Gastric cancer is the fourth most common cancer and the second leading cause of cancer-related deaths worldwide. Gastric cancer is characterized by high levels of invasion and metastasis. Increasing attention is being focused on discovering molecular markers for the diagnosis of gastric cancer and for predicting its prognosis. The objective of the present study was to evaluate Nurr1 expression in gastric cancer and to assess its correlation with clinicopathological parameters and prognosis in gastric cancer patients.
  
  
  METHODS
  Tissue samples were obtained from 120 gastric cancer patients. We investigated Nurr1 expression in human normal and gastric cancer tissues using real-time reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. We determined the association between Nurr1 and recurrence, prognosis and patient clinicopathological parameters. Univariate and multivariate survival analyses with a Cox's proportional hazards regression model were used to identify independent factors related to recurrence and prognosis.
  
  
  RESULTS
  The immunohistochemical, qRT-PCR and western blot analyses revealed that Nurr1 expression was increased in gastric cancer tissues compared with normal gastric tissue (P < 0.05). Nurr1 expression was significantly correlated with the tumor size, depth of tumor invasion, lymph node metastasis, recurrence, and distant metastasis of gastric cancer (P < 0.05). Moreover, Nurr1-high patients also exhibited poorer overall survival (OS) and disease-free survival compared with Nurr1-low patients (P < 0.01). The univariate and multivariate survival analyses suggested that Nurr1 expression (P = 0.011), histology (P = 0.018), depth of tumor invasion (P = 0.037), and presence of lymph node metastasis (P = 0.031) were independent prognostic factors for recurrence. In addition, Nurr1 expression (P = 0.007), depth of tumor invasion (P = 0.014), lymph node metastasis (P = 0.044), distant metastasis (P = 0.023), and recurrence (P = 0.011) were independent prognostic factors of OS in gastric cancer patients.
  
  
  CONCLUSIONS
  The Nurr1 protein may be useful as a marker of recurrence, metastasis, and poor prognosis following curative resection in patients with gastric cancer.
authors.affiliation: Department of Surgical Operation, Dalian Medical University, Dalian, 116044, People's Republic of China. gzq19871214@163.com.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, People's Republic of China. zushanghai@163.com.
authors.forename: G
authors.initials: G
authors.lastname: Zu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People's Republic of China. jane1987@126.com.
authors.forename: T
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, The Maternity and Child Care Institute of Dalian Xigang District, Dalian, 116021, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People's Republic of China. fishflowers@hotmail.com.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden; D055815:Young Adult
chemical_list: C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2
keywords: Gastric cancer; Immunohistochemistry; Metastasis; Nurr1; Prognosis