Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Hepatobiliary Pancreat Dis Int. 2012 Apr;11(2):177-84. doi: 10.1016/s1499-3872(12)60145-3.
In vitro experiments and mice models have confirmed the importance of Sprouty 2 (Spry2) in inhibiting tumorigenesis and the progression of human cancer. However, the prognostic value of Spry2 in cancer patients remains unknown. This study is aimed to investigate the clinical relevance and prognostic significance of Spry2 expression in patients with hepatocellular carcinoma (HCC).
With samples from 240 randomly-selected HCC patients who underwent surgery, immunohistochemistry was used to investigate Spry2 expression on tissue microarrays. The correlation of Spry2 expression with survival was estimated by the Kaplan-Meier method and univariate/multivariate Cox proportional hazard regression analysis. Spry2, ERK and phospho-ERK expression in HCC cell lines was detected by Western blotting.
Among the patients, 86.3% (207 of 240) exhibited down-regulation of Spry2 expression. Patients negative for Spry2 showed poorer survival (P=0.002) and increased recurrence (P=0.003). Multivariate analysis further established Spry2 as an independent predictor of postoperative recurrence in HCC patients (HR=1.47; 95% CI, 1.02-2.08; P=0.037). Down-regulation of Spry2 was associated with highly malignant phenotypes like vascular invasion and advanced tumor stages, and was positively correlated with the metastatic potential of HCC cell lines.
In the era of molecular targeted therapy, the expression of Spry2 in HCC may have relevant clinical significance and turn out to be a key factor in prognostic assessment and in treatment planning.
体外实验和小鼠模型已经证实 Sprouty2（Spry2）在抑制肿瘤发生和人类癌症进展中的重要性。然而，Spry2 在癌症患者中的预后价值尚不清楚。本研究旨在探讨 Spry2 在肝细胞癌（HCC）患者中的临床相关性和预后意义。
采用 240 例随机选择的 HCC 手术患者的样本，通过组织微阵列免疫组织化学检测 Spry2 表达。Kaplan-Meier 方法和单因素/多因素 Cox 比例风险回归分析估计 Spry2 表达与生存的相关性。通过 Western blot 检测 HCC 细胞系中 Spry2、ERK 和磷酸化 ERK 的表达。
在 240 例患者中，86.3%（207/240）表现出 Spry2 表达下调。Spry2 阴性患者的生存较差（P=0.002），复发率增加（P=0.003）。多因素分析进一步确立 Spry2 是 HCC 患者术后复发的独立预测因子（HR=1.47；95%CI，1.02-2.08；P=0.037）。Spry2 下调与血管侵犯和晚期肿瘤分期等高度恶性表型相关，与 HCC 细胞系的转移潜力呈正相关。
在分子靶向治疗时代，HCC 中 Spry2 的表达可能具有相关的临床意义，并成为预后评估和治疗计划的关键因素。
