Li Zhi, Li Ao-Di, Xu Lu, Bai De-Wei, Hou Ke-Zuo, Zheng Hua-Chuan, Qu Xiu-Juan, Liu Yun-Peng
Department of Medical Oncology, The First Hospital, China Medical University, Shenyang, Liaoning Province, China.
Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province.
Oncotarget. 2016 Oct 25;7(43):70211-70222. doi: 10.18632/oncotarget.12191.
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.
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.
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.
Increased SPARC expression in GC led to a worse clinical outcome of patients and might induce Adr sensitivity of GC cells.
富含半胱氨酸的酸性分泌蛋白（SPARC）在胃癌（GC）中的预后作用仍存在争议。我们利用手术切除样本、在线基因集GSE62254和细胞系SGC7901，研究了SPARC在GC中的临床意义、生存相关性及潜在功能。
基于目前的免疫组化评估，SPARC的高免疫染色与肿瘤分化显著相关（P = 0.004），并独立预测总生存期（OS）较短（HR = 1.446，P = 0.022）。通过1000次自抽样和时间依赖性受试者工作特征（ROC）曲线进一步验证了结果的准确性。荟萃分析（合并HR = 1.60，95%CI：1.01 - 2.53）证实SPARC可作为GC患者OS降低的预测指标。此外，基因集富集分析（GSEA）揭示了SPARC表达增强与阿霉素（Adr）敏感性之间的关联，随后通过比较细胞实验得到证实，如SGC7901和SGC7901/Adr细胞系的蛋白水平分析。
采用免疫组化（IHC）方法检测137例GC病例中SPARC的表达。基于截至2016年3月在PubMed上发表的5篇英文研究进行荟萃分析。使用在线数据集GSE62254和源自分子特征数据库（MSigDB）的GC相关功能基因集进行GSEA。进行蛋白质印迹法比较胃癌SGC7901细胞系和阿霉素耐药SGC7901/Adr细胞系之间的蛋白水平差异。采用MTT法确认SPARC对阿霉素敏感性的诱导作用。
GC中SPARC表达增加导致患者临床结局较差，并可能诱导GC细胞对阿霉素敏感。
