title: Sphingosine kinase 1 and cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  Sphingosine kinase 1 (SK1) is a key regulator of the dynamic ceramide/sphingosine 1-phosphate rheostat balance and important in the pathological cancer genesis, progression, and metastasis processes. Many studies have demonstrated SK1 overexpressed in various cancers, but no meta-analysis has evaluated the relationship between SK1 and various cancers.
  
  
  METHODS
  We retrieved relevant articles from the PubMed, EBSCO, ISI, and OVID databases. A pooled odds ratio (OR) was used to assess the associations between SK1 expression and cancer; hazard ratios (HR) were used for 5-year and overall survival. Review Manager 5.0 was used for the meta-analysis, and publication bias was evaluated with STATA 12.0 (Egger's test).
  
  
  RESULTS
  Thirty-four eligible studies (n=4,673 patients) were identified. SK1 positivity and high expression were significantly different between cancer, non-cancer, and benign tissues. SK1 mRNA and protein expression levels were elevated in the cancer tissues, compared with the normal tissues. SK1 positivity rates differed between various cancer types (lowest [27.3%] in estrogen receptor-positive breast cancer and highest [82.2%] in tongue squamous cell carcinoma). SK1 positivity and high expression were associated with 5-year survival; the HR was 1.86 (95% confidence interval [CI], 1.18-2.94) for breast cancer, 1.58 (1.08-2.31) for gastric cancer, and 2.68 (2.10-3.44) for other cancers; the total cancer HR was 2.21 (95% CI, 1.83-2.67; P < 0.00001). The overall survival HRs were 2.09 (95% CI, 1.35-3.22), 1.56 (1.08-2.25), and 2.62 (2.05-3.35) in breast, gastric, and other cancers, respectively. The total effect HR was 2.21 (95% CI, 1.83-2.66; P < 0.00001).
  
  
  CONCLUSIONS
  SK1 positivity and high expression were significantly associated with cancer and a shorter 5-year and overall survival. SK1 positivity rates vary tremendously among the cancer types. It is necessary to further explore whether SK1 might be a predictive biomarker of outcomes in cancer patients.
authors.affiliation: Department of Emergency, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, School of Public Health, Jilin Medical College, Jilin, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Emergency, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of Emergency, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
authors.forename: Shiping
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Emergency, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Emergency, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zeng
mesh_terms: D014408:Biomarkers, Tumor; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism*; D016016:Proportional Hazards Models; D017594:Publication Bias; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D014408:Biomarkers, Tumor; D017853:Phosphotransferases (Alcohol Group Acceptor); D012333:RNA, Messenger; D000099157:Sphingosine Kinase