title: SPARC expression in gastric cancer predicts poor prognosis: Results from a clinical cohort, pooled analysis and GSEA assay.
abstract: BACKGROUND
  The prognostic role of Secreted Protein Acidic and Rich in Cysteine (SPARC) in gastric cancer (GC) remains controversial. We investigated the clinical significance, the survival relevance, and potential function of SPARC in GC with resected samples, online gene set GSE62254, and cell line SGC7901.
  
  
  RESULTS
  High immunostaining of SPARC significantly correlated with tumor differentiation (P = 0.004), and independently predicted shorter overall survival (OS) (HR = 1.446, P = 0.022), based on the current IHC evaluation. The accuracy of the results was further validated with 1000 times bootstrapping and the time-dependent receiver-operating characteristics (ROC) curves. The meta-analysis (pooled HR = 1.60, 95% CI: 1.01-2.53) confirmed SPARC as the predictor for reduced OS in GC. Moreover, the association between enhanced SPARC expression and Adriamycin (Adr) sensitivity was revealed by GSEA, and then confirmed by comparative cellular experiments, such as the protein level analysis of SGC7901and SGC7901/Adr cell line.
  
  
  METHODS
  Immunohistochemistry (IHC) method was used to detect SPARC expression in 137 GC cases. Meta-analysis was performed based on 5 studies published in English on PubMed up to March 2016. GSEA was performed using online data set GSE62254 and GC-related functional gene sets derived from molecular signatures database (MSigDB). Western Blot was carried out to compare protein-level differences between gastric carcinoma SGC7901 cell line and Adr resistant SGC7901/Adr cell line. MTT assay was done to confirm the induction of SPARC on Adr sensitivity.
  
  
  CONCLUSIONS
  Increased SPARC expression in GC led to a worse clinical outcome of patients and might induce Adr sensitivity of GC cells.
authors.affiliation: Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, Liaoning Province, China.|Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, Liaoning Province, China.|Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province.
authors.forename: Ao-Di
authors.initials: AD
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, Liaoning Province, China.|Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province.
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, Liaoning Province, China.|Department of Cell Biological Treatment Ward, Dalian Centre Hospital, Dalian, Liaoning Province, China.|Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province.
authors.forename: De-Wei
authors.initials: DW
authors.lastname: Bai
authors.affiliation: Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, Liaoning Province, China.|Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province.
authors.forename: Ke-Zuo
authors.initials: KZ
authors.lastname: Hou
authors.affiliation: Life Science Institute of Jinzhou Medical University, Jinzhou, Liaoning Province, China.
authors.forename: Hua-Chuan
authors.initials: HC
authors.lastname: Zheng
authors.affiliation: Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, Liaoning Province, China.|Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Qu
authors.affiliation: Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, Liaoning Province, China.|Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015676:Osteonectin / Q000032:analysis*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology
chemical_list: D015676:Osteonectin; C577241:SPARC protein, human; D004317:Doxorubicin
keywords: GSEA; SPARC; gastric cancer; immunohistochemistry; prognosis