△Np73基因在人非小细胞肺癌中的转录表达及其临床意义

Expression of ΔNp73 in human NSCLC and clinical implication

背景和目的ΔNp73是p53基因家族新成员p73的异构体,研究表明ΔNp73因为N末端转录活化区缺失致转录活化功能完全丧失,对p53和全长型p73的转录活化和促凋亡活性有明显的负调节作用。本研究旨在探讨人非小细胞肺癌组织中ΔNp73转录表达及其与患者临床病理特征之间的关系,分析其对肺癌患者预后的意义。方法采用半定量逆转录多聚酶链反应技术(RT-PCR)检测40例非小细胞肺癌癌组织及癌旁肺组织ΔNp73mRNA的表达,结合其临床病理特征,统计分析ΔNp73在肺癌组织中表达的意义。结果51例非小细胞肺癌癌组织中有32例(62.7%)呈ΔNp73mRNA高表达,而在癌旁肺组织中低表达。ΔNp73的表达与肺癌的临床TNM分期有密切关系(P=0.046),但与患者年龄、性别、分化程度和病理学类型无显著相关性。ΔNp73mRNA高表达的患者较低表达的患者术后生存期短,预后差(P<0.001)。结论ΔNp73基因在人非小细胞肺癌癌组织中的转录表达较对应癌旁肺组织明显升高,并与患者临床分期和预后相关。ΔNp73基因的转录表达情况可作为非小细胞肺癌预后判断的参考指标之一。

Background and objective △Np73 is an isoform of the p53 homologue p73, which lacks an NH2-terminal transactivation domain and antagonizes the induction of gene expression by p53 and p73. The aim of this study is to investigate the expression of △Np73 mRNA in non-small cell lung cancer （NSCLC） and to analyse its relations with clinicopathologic factors and prognosis. Methods Semiquantitative reverse transcriptase polymerase chain reaction （RT-PCR） was used to detect the expression of △Np73 mRNA in 40 resected NSCLC specimens with the neighboring noncancerous tissue. The significance of △Np73 mRNA expression was analyzed statistically. Results △Np73 mRNA was highly expressed in lung cancer tissues （62.7%, 32/ 51） while negative in neighboring noncancerous tissue. The expression of △Np73 mRNA was associated with pathological TNM stage （P=0. 046）, but not associated with age, gender, histological type and differentiation status. Survival of patients with high △Np73 mRNA was significantly poorer than those with low △Np73 mRNA levels （P〈0. 001）. Multivariate analysis revealed that △Np73 mRNA levels were a significant prognostic factor, independent of the other conventional prognostic factors. Conclusion NSCLC has overexpression of △Np73 mRNA, which is closely related to TNM stages and prognosis of patients with NSCLC. These results suggest that measurement of △Np73 mRNA levels in tumor tissues might be useful as a promising predictor for the prognosis of patients with NSCLC.