Hepato-gastroenterology and Endemic Medicine Department, Cairo University, Cairo, Egypt.
Medical Biochemisry Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
J Gastroenterol Hepatol. 2019 Aug;34(8):1424-1431. doi: 10.1111/jgh.14541. Epub 2018 Dec 9.
Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein involved in extracellular matrix remodeling, which regulates cell growth. It could be involved in hepatic fibrogenesis related to chronic inflammations, hepatocellular carcinoma (HCC) angiogenesis, and tumor progression. We aimed to study the expressions of single nucleotide polymorphisms in the SPARC gene and their impact on susceptibility and survival of HCC patients.
We conducted a case-control study on 200 HCC patients and 50 matched healthy controls. All patients were subjected to laboratory investigations, ultrasound, and real-time polymerase chain reaction to detect the genetic polymorphisms (rs3210714, rs11950384, and rs7719521) in the SPARC gene in the blood.
One hundred sixty (80%) patients were men with a mean age of 43 years. The SPARC gene showed a significant higher prevalence of rs3210714 mutation (i.e. AA or AG) and a significant lower prevalence of rs11950384 mutation (i.e. AA or AC) among HCC patients in comparison with controls (83% vs 22%, P ≤ 0.001) and (65.5 vs 86%, P = 0.005), respectively, while rs7719521 mutation did not reach significance. On univariate and multivariate analyses, elder age and having at least one copy of the mutant rs3210714 were associated with a significantly increased risk of HCC (P < 0.001 for both), whereas the presence of at least one copy of the mutant rs11950384 carried a significantly reduced risk of having HCC (P < 0.01). Overall survival did not differ significantly between any of the SPARC gene mutation groups.
The SPARC gene polymorphisms had a diverse impact on the susceptibility of HCC due to its ability to inhibit or promote tumor progression. SPARC gene polymorphisms were not related to survival of our HCC patients, and probably, this needs further analysis of other SPARC gene nucleotides.
富含半胱氨酸的酸性分泌蛋白（SPARC）是一种参与细胞外基质重塑的糖蛋白，它调节细胞生长。它可能参与与慢性炎症相关的肝纤维化、肝细胞癌（HCC）血管生成和肿瘤进展。我们旨在研究 SPARC 基因中单核苷酸多态性的表达及其对 HCC 患者易感性和生存的影响。
我们对 200 例 HCC 患者和 50 例匹配的健康对照进行了病例对照研究。所有患者均进行了实验室检查、超声和实时聚合酶链反应，以检测血液中 SPARC 基因的遗传多态性（rs3210714、rs11950384 和 rs7719521）。
160 例（80%）患者为男性，平均年龄为 43 岁。与对照组相比，HCC 患者 SPARC 基因 rs3210714 突变（即 AA 或 AG）的发生率显著升高，rs11950384 突变（即 AA 或 AC）的发生率显著降低（83%比 22%，P≤0.001）和（65.5%比 86%，P=0.005），而 rs7719521 突变无统计学意义。单因素和多因素分析显示，年龄较大和至少携带一份 rs3210714 突变与 HCC 的发生风险显著增加相关（均 P<0.001），而至少携带一份 rs11950384 突变与 HCC 的发生风险显著降低相关（P<0.01）。任何 SPARC 基因突变组的总生存率均无显著差异。
由于 SPARC 基因能够抑制或促进肿瘤进展，其多态性对 HCC 的易感性有不同的影响。SPARC 基因多态性与我们的 HCC 患者的生存无关，可能需要进一步分析其他 SPARC 基因核苷酸。
