Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Mol Cancer. 2013 Oct 20;12(1):125. doi: 10.1186/1476-4598-12-125.
The lung squamous cell carcinoma survival rate is very poor despite multimodal treatment. It is urgent to discover novel candidate biomarkers for prognostic assessment and therapeutic targets to lung squamous cell carcinoma (SCC).
Herein a two-dimensional gel electrophoresis and ESI-Q-TOF MS/MS-based proteomic approach was used to identify differentially expressed proteins between lung SCC and adjacent normal tissues. 31 proteins with significant alteration were identified. These proteins were mainly involved in metabolism, calcium ion binding, signal transduction and so on. Cathepsin B (CTSB) was one of the most significantly altered proteins and was confirmed by western blotting. Immunohistochemistry showed the correlation between higher CTSB expression and lower survival rate. No statistically significant difference between CTSB-shRNA treated group and the controls was observed in tumor volume, tumor weight, proliferation and apoptosis. However, the CTSB-shRNA significantly inhibited tumor metastases and prolonged survival in LL/2 metastatic model. Moreover, CTSB, Shh and Ptch were up-regulated in patients with metastatic lung SCC, suggesting that hedgehog signaling might be activated in metastatic lung SCC which could affect the expression of CTSB that influence the invasive activity of lung SCC.
These data suggested that CTSB might serve as a prognostic and therapeutic marker for lung SCC.
尽管采用了多种治疗方法,肺鳞状细胞癌的存活率仍然很差。迫切需要发现新的候选生物标志物,用于肺鳞状细胞癌(SCC)的预后评估和治疗靶点。
本研究采用二维凝胶电泳和 ESI-Q-TOF MS/MS 蛋白质组学方法,鉴定肺 SCC 和相邻正常组织之间差异表达的蛋白质。鉴定出 31 种具有显著改变的蛋白质。这些蛋白质主要参与代谢、钙离子结合、信号转导等过程。组织蛋白酶 B(CTSB)是变化最显著的蛋白质之一,并通过 Western blot 得到验证。免疫组织化学显示 CTSB 表达较高与生存率较低之间存在相关性。CTSB-shRNA 处理组与对照组在肿瘤体积、肿瘤重量、增殖和凋亡方面无统计学差异。然而,CTSB-shRNA 显著抑制了 LL/2 转移模型中的肿瘤转移并延长了生存期。此外,转移性肺 SCC 患者中 CTSB、Shh 和 Ptch 表达上调,提示转移性肺 SCC 中 Hedgehog 信号通路可能被激活,可能影响 CTSB 的表达,从而影响肺 SCC 的侵袭活性。
这些数据表明 CTSB 可能作为肺 SCC 的预后和治疗标志物。