title: NPTX1 is a novel epigenetic regulation gene and associated with prognosis in lung cancer.
abstract: BACKGROUND
  CpG island hypermethylation of gene promoters is a well-known mechanism of epigenetic regulation of tumor related-genes and is directly linked to lung carcinogenesis. Alterations in the pattern of methylation of the NPTX1 gene have not yet been studied in detail in human lung cancer.
  
  
  METHODS
  Methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) were used to analyze promoter methylation status, and real-time quantitative reverse transcription-PCR (qRT-PCR) examined mRNA levels. Subsequently, we compared the methylation profile of NPTX1 in samples of neoplastic and non-neoplastic lung tissue taken from the same patients by using quantitative methylation specific PCR (QMSP).
  
  
  RESULTS
  CpG island hypermethylation in promoter of NPTX1 was confirmed in lung cancer cell lines. A significant increase in NPTX1 methylation was identified in lung cancer specimens compared to adjacent noncancerous tissues and that it was negatively correlated with its mRNA expression. The overall survival time among patients carrying methylated NPTX1 tumors was significantly shorter as compared to those with unmethylated NPTX1 tumors (P = 0.011). Moreover, methylation of NPTX1 gene was found to be an independent prognostic factor for poor overall survival based on multivariate analysis models (p = 0.021), as was age ≥60 years old (p = 0.012) and TNM stage (p < 0.001).
  
  
  CONCLUSIONS
  These results suggest that NPTX1 hypermethylation and consequent mRNA changes might be an important molecular mechanism in lung cancer. Epigenetic alterations in NPTX1 may serve as potential diagnostic and prognostic biomarkers in lung cancer.
authors: Department of Medicine, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China.
authors: Chengzhi
authors: C
authors: Zhou
authors: Department of Medicine, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China.
authors: Yinyin
authors: Y
authors: Qin
authors: Department of Medicine, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China.
authors: Zhanhong
authors: Z
authors: Xie
authors: Department of Medicine, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China.
authors: Jiexia
authors: J
authors: Zhang
authors: Department of Medicine, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China.
authors: Mingou
authors: M
authors: Yang
authors: Department of Medicine, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China. Electronic address: syli696@hotmail.com.
authors: Shiyue
authors: S
authors: Li
authors: Department of Medicine, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China. Electronic address: rcchen23@hotmail.com.
authors: Rongchang
authors: R
authors: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002097:C-Reactive Protein / Q000235:genetics*; D045744:Cell Line, Tumor; D002681:China / Q000453:epidemiology; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015995:Prevalence; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate; D000099153:Pentraxins
chemical_list: D014408:Biomarkers, Tumor; D002097:C-Reactive Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D000099153:Pentraxins
keywords: Lung cancer; NPTX1; Prognosis; Promoter methylation