肺癌FHIT基因表达下降的临床病理生理意义及与肿瘤细胞增殖、凋亡的关系研究

Reduction of FHIT gene expression in primary lung cancer: relationship with the proliferation and apoptosis of tumor cell

目的 研究 FHIT(fragile histidine triad)基因表达下降与人肺癌临床病理生理特征和预后的关系 ,探讨 FHIT基因表达与细胞增殖和凋亡的相关性。方法 应用免疫组化法检测了 16 6例肺癌组织标本和 37例肺良性病变组织中 FHIT基因及 Ki- 6 7的表达水平 ,应用脱氧核糖核酸末端转移酶介导的缺口末端标记法检测其细胞凋亡指数。结果 (1)肺癌组织中 FHIT基因表达水平显著低于肺良性病变组织(P<0 .0 1) ;(2 )肺癌组织中 FHIT基因表达水平降低与肺癌组织学类型、细胞分化程度 ,患者 P- TNM分期、淋巴结转移程度存在相关性 (P<0 .0 5 ) ;(3)肺癌组织中 FHIT基因表达水平降低可能与肺癌患者长期大量吸烟有关 (P<0 .0 1) ;(4) FHIT基因低表达组肺癌患者的术后长期生存率显著低于高表达组 (P<0 .0 5 ) ;(5 ) FHIT基因表达水平降低与肺癌细胞的增殖活跃及凋亡受抑可能存在一定程度的相关性 (P<0 .0 1)。结论 FHIT基因可能参与了对肺癌肿瘤细胞增殖和凋亡的调节 ,其表达下降可能与肺癌的发生、发展过程有关。

Objective: To investigate the role of FHIT(fragile histidine triad) gene in oncogenesis and progression of human lung cancer and explore the relationship of FHIT gene expression with the proliferation and apoptosis of tumor cells. Methods: The expression of FHIT gene and that of Ki-67 were detected in 166 lung cancer samples and 37 lung benign lesion tissues as control by immunohistochemistry, and the apoptotic level of tumor cell was detected by terminal deoxynucl neotidyl transferase mediated dUTP nick end labelling(TUNEL). Results: (1)The expression level of FHIT gene was found to be significantly lower in lung cancer tissues than in benign lesion tissues (P<0.01); (2)The expression level of FHIT gene was closely related to histological classification, cancer cell differentiation, P-TNM stages and lymph node involvement in lung cancer patients(P<0.05); (3)Lasting and heavy smoking might be one of the important reasons of reduction of FHIT gene expression in lung cancer patients; (4)The postoperative survival time of patients in high FHIT expression group was significantly longer than those in low expression group(P<0.05); (5)The reduction of FHIT gene expression might be related with the over-proliferation and suppression of apoptosis of lung cancer cell(P<0.01). Conclusion: FHIT gene may play a role in the regulation of proliferation and apoptosis of lung cancer cell. And reduction of FHIT gene expression may be related to the pathogenesis and development of lung cancer.