Identification of PRDX4 and P4HA2 as Metastasis-Associated Proteins in Oral Cavity Squamous Cell Carcinoma by Comparative Tissue Proteomics of Microdissected Specimens Using iTRAQ Technology
Identification of PRDX4 and P4HA2 as Metastasis-Associated Proteins in Oral Cavity Squamous Cell Carcinoma by Comparative Tissue Proteomics of Microdissected Specimens Using iTRAQ Technology
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DOI：
10.1021/pr200311p
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发表时间：
2011-11-01
影响因子：
4.4
通讯作者：
Chi, Lang-Ming
中科院分区：
文献类型：
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作者：
Chang, Kai-Ping;Yu, Jau-Song;Chi, Lang-Ming
颈淋巴结转移是口腔鳞癌发生的主要危险因素。在这里，我们使用了iTRAQ为基础的定量蛋白质组学方法，以确定蛋白质之间的差异表达显微切割的原发性和转移性口腔鳞癌肿瘤。通过免疫组织化学在组织切片中检查所选择的候选者，并使用RNA干扰研究它们在OSCC细胞功能中的作用。74个差异表达蛋白在淋巴结转移，包括PRDX 4和P4 HA 2，被确定。免疫组化分析显示PRDX 4和P4 HA 2在肿瘤细胞中的表达水平显著高于邻近非肿瘤上皮细胞（分别为P < 0.0001和P < 0.0001），并且在31例淋巴结转移瘤中的表达水平甚至高于相应的原发肿瘤（分别为P = 0.060和P = 0.002）。PRDX 4和P4 HA 2的过表达与pN阳性状态显著相关（分别为P = 0.048和P = 0.021）。在单变量和多变量分析中，PRDX 4过表达是疾病特异性生存的重要预后因素（分别为P = 0.034和P = 0.032）。此外，在OEC-M1细胞中，在用特异性干扰RNA体外敲低PRDX 4和P4 HA 2后，细胞迁移和侵袭性减弱。通过我们的方法，可以确定新的与转移相关的口腔鳞癌预后标志物。
Cervical lymph node metastasis represents the major prognosticator for oral cavity squamous cell carcinoma (OSCC). Here, we used an iTRAQ-based quantitative proteomic approach to identify proteins that are differentially expressed between microdissected primary and metastatic OSCC tumors. The selected candidates were examined in tissue sections via immunohistochemistry, and their roles in OSCC cell function investigated using RNA interference. Seventy-four differentially expressed proteins in nodal metastases, including PRDX4 and P4HA2, were identified. Immunohistochemical analysis revealed significantly higher levels of PRDX4 and P4HA2 in tumor cells than adjacent non-tumor epithelia (P < 0.0001 and P < 0.0001, respectively), and even higher expression in the 31 metastatic tumors of lymph nodes, compared to the corresponding primary tumors (P = 0.060 and P = 0.002, respectively). Overexpression of PRDX4 and P4HA2 was significantly associated with positive pN status (P = 0.048 and P = 0.021, respectively). PRDX4 overexpression was a significant prognostic factor for disease-specific survival in both univariate and multivariate analyses (P = 0.034 and P = 0.032, respectively). Additionally, cell migration and invasiveness were attenuated in OEC-M1 cells upon in vitro knockdown of PRDX4 and P4HA2 with specific interfering RNA. Novel metastasis-related prognostic markers for OSCC could be identified by our approach.