SPARC expression in gastric cancer predicts poor prognosis: Results from a clinical cohort, pooled analysis and GSEA assay

// Zhi Li 1, 4 , Ao-Di Li 1, 4 , Lu Xu 1, 4 , De-Wei Bai 1, 2, 4 , Ke-Zuo Hou 1, 4 , Hua-Chuan Zheng 3 , Xiu-Juan Qu 1, 4 , Yun-Peng Liu 1, 4 1 Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, Liaoning Province, China 2 Department of Cell Biological Treatment Ward, Dalian Centre Hospital, Dalian, Liaoning Province, China 3 Life Science Institute of Jinzhou Medical University, Jinzhou, Liaoning Province, China 4 Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, Shenyang, Liaoning, China Correspondence to: Yun-Peng Liu, email: cmuliuyunpeng@hotmail.com Xiu-Juan Qu, email: qu_xiujuan@hotmail.com Keywords: SPARC, gastric cancer, prognosis, immunohistochemistry, GSEA Received: April 16, 2016      Accepted: September 02, 2016      Published: September 22, 2016 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. Materials and 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.