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作 者:田聪[1] 汤丽娜[2] 林峰[2] 沈赞[2] 陈杰[3] 姚阳[2] 闵大六[2]
机构地区:[1]苏州大学医学部研究生院,江苏苏州215131 [2]上海交通大学附属第六人民医院肿瘤内科,上海200233 [3]上海交通大学附属第六人民医院病理科,上海200233
出 处:《中国癌症杂志》2014年第1期1-7,共7页China Oncology
基 金:国家自然科学基金面上项目资助(No:81172548)
摘 要:背景与目的:p21活化激酶5(p21-activated kinase 5,PAK5)为PAKs家族中新近发现的成员,在细胞骨架重组,细胞生长、增殖、分化,基因转录及细胞凋亡等一系列的细胞功能中发挥重要作用。近来有研究发现PAK5参与了胃癌、肠癌等恶性肿瘤的发生发展过程。本研究旨在探讨PAK5在人骨肉瘤组织中的表达及其与骨肉瘤患者预后的关系。方法:应用免疫组化方法检测92例骨肉瘤活检样本石蜡组织中PAK5蛋白的表达,33例骨巨细胞瘤样本作为阴性对照,并分析PAK5表达与骨肉瘤患者临床参数及生存之间的关系。结果:骨肉瘤组织中PAK5蛋白表达阳性率为71.7%(66/92),骨巨细胞瘤中未见PAK5表达(0/33)。PAK5表达与患者的性别、年龄、肿瘤部位、肿瘤大小、组织学类型、局部复发等无关,而与Enneking分期、肿瘤坏死率和肺转移相关,且PAK5高表达能降低化疗的有效率。单因素分析表明,肿瘤大小、Enneking分期、局部复发、肺转移及PAK5表达水平是影响骨肉瘤患者预后的因素。多因素分析显示,PAK5表达水平(P=0.001)及肺转移(P=0.015)是影响骨肉瘤预后相关的独立的重要因素。结论:PAK5表达水平与Enneking分期、肿瘤坏死率和肺转移相关;PAK5的表达可作为骨肉瘤预后预测的指标;PAK5高表达能降低化疗的有效率。Background and purpose: p21-activated kinase 5 (PAK5) is a recently identified member of PAKs that regulate many intracellular processes such as cytoskeleton remodeling, cell proliferation, cell differentiation, gene transcription and cell apoptosis. Recently, studies found that PAK5 was overexpressed in some cancer such as gastric and colon cancer. However, the expression status and biological function of PAK5 in osteosarcoma are not clearly known. The objective of this study was to investigate the expression of PAK5 in osteosarcoma tissue and their relationships with the prognosis of osteosarcoma. Methods: The expression of PAK5 was detected by using immunohistochemical method in 92 specimens of human osteosarcoma tissues and 33 cases of osteoclastoma tissue, respectively. Results: The positive rate of PAK5 was 71.7% (66/92) in all the 92 cases of osteosarcoma. PAK5 expressions were not related to clinical variables such as gender, age, tumor location, tumor size, histological type and local recurrence, but significantly related to Enneking grade, tumor cell necrosis rate and lung metastasis, and the high expression of PAK5 may reduce the efficiency of chemotherapy. Survival analysis indicated that high expression of PAK5 correlated with poor prognosis of patients with osteosarcoma. Univariate survival analysis showed that the significant prognostic factors were tumor size, Enneking grade, local recurrence, lung metastasis and expression levels of PAK5. COX multivariate regression identified that the PAK5 expression levels (P=0.001) and lung metastasis (/^-0.015) were independent prognostic factors of patients with osteosarcoma. Conclusion: The positive expressions of PAK5 closely correlate with Enneking grade, tumor cell necrosis rate and lung metastasis. Detection of PAK5 may be used as a molecular marker for prognosis of osteosarcoma. The high expression of PAK5 may reduce the efficiency of chemotherapy.
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