title: Correlation of S1P1 and ERp29 expression to progression, metastasis, and poor prognosis of gallbladder adenocarcinoma.
abstract: BACKGROUND
  Gallbladder cancer (GBC) is one of the most aggressive malignant neoplasms with an extremely poor prognosis. Early diagnosis significantly increases the survival rate. The present study was undertaken to evaluate the diagnostic and prognostic value of sphingosine-1-phosphate receptor 1 (S1P1) and endoplasmic reticulum protein 29 (ERp29) in benign and malignant gallbladder lesions and to develop a possible alternative treatment for GBC.
  
  
  METHODS
  A total of 100 gallbladder adenocarcinoma, 46 peritumoral, 30 gallbladder adenomatous, 15 gallbladder polyp, and 35 chronic cholecystitis tissues were included. S1P1 and ERp29 expressions were evaluated by immunohistochemistry. The correlation between S1P1 and ERp29 expression and tumor pathological features and prognosis was analyzed.
  
  
  RESULTS
  S1P1 positive rate was significantly higher in gallbladder adenocarcinomas than that in peritumoral, adenomatous, polyp, and chronic cholecystitis tissues. On the contrary, ERp29 positive rate was significantly lower in adenocarcinomas than that in peritumoral, adenomatous, polyp, and chronic cholecystitis tissues. Benign lesions with positive S1P1 or negative ERp29 expression showed moderate or severe atypical hyperplasia in the gallbladder epithelium. The overexpression of S1P1 or non-expression of ERp29 was significantly associated with tumor differentiation, tumor mass, lymph node metastasis, and adenocarcinoma invasion. Univariate Kaplan-Meier analysis showed that the elevated S1P1 (P=0.008) or absence of ERp29 (P=0.043) was closely associated with decreased survival rate. Multivariate Cox regression analysis showed that S1P1 positive (P=0.004) or ERp29 negative (P=0.029) was an independent predictor of poor prognosis in gallbladder adenocarcinoma.
  
  
  CONCLUSIONS
  S1P1 overexpression or ERp29 absence is related to the carcinogenesis and progression, and may be potential biomarkers for early detection of gallbladder adenocarcinoma.
authors.affiliation: Department of Geriatric Surgery, Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha 410011, China.
authors.forename: Lian-Wen
authors.initials: LW
authors.lastname: Yuan
authors.forename: Dong-Cai
authors.initials: DC
authors.lastname: Liu
authors.forename: Zhu-Lin
authors.initials: ZL
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000556:secondary; D000236:Adenoma / Q000737:chemistry; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D002764:Cholecystitis / Q000378:metabolism; D002908:Chronic Disease; D015536:Down-Regulation; D055088:Early Detection of Cancer; D005260:Female; D005706:Gallbladder Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D006360:Heat-Shock Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011127:Polyps / Q000737:chemistry; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D049349:Receptors, Lysosphingolipid / Q000032:analysis*; D012307:Risk Factors; D000081025:Sphingosine-1-Phosphate Receptors; D013997:Time Factors; D047368:Tumor Burden; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C491738:ERP29 protein, human; D006360:Heat-Shock Proteins; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D000081025:Sphingosine-1-Phosphate Receptors