SPARC expression in gastric cancer predicts poor prognosis: Results from a clinical cohort, pooled analysis and GSEA assay
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Zhi Li1,4, Ao-Di Li1,4, Lu Xu1,4, De-Wei Bai1,2,4, Ke-Zuo Hou1,4, Hua-Chuan Zheng3, Xiu-Juan Qu1,4, Yun-Peng Liu1,4
1Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, Liaoning Province, China
2Department of Cell Biological Treatment Ward, Dalian Centre Hospital, Dalian, Liaoning Province, China
3Life Science Institute of Jinzhou Medical University, Jinzhou, Liaoning Province, China
4Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, Shenyang, Liaoning, China
Yun-Peng Liu, email: email@example.com
Xiu-Juan Qu, email: firstname.lastname@example.org
Keywords: SPARC, gastric cancer, prognosis, immunohistochemistry, GSEA
Received: April 16, 2016 Accepted: September 02, 2016 Published: September 22, 2016
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.
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