收稿日期: 2020-01-20
网络出版日期: 2020-06-25
基金资助
上海市嘉定区卫健委课题(2017KY02)
The prognostic value of Beclin-1 and Bcl-2 and its relationship with pathological characteristics in patients with non-small cell lung cancer
Received date: 2020-01-20
Online published: 2020-06-25
目的: 检测非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中Beclin-1和Bcl-2蛋白的表达,分析其与患者临床病理特征及预后间的关系,探讨Beclin-1和Bcl-2蛋白检测在NSCLC疾病发展及预后评估中的应用价值。方法: 采用免疫组织化学(免疫组化)染色法检测120例经外科手术切除的NSCLC组织及配对癌旁组织中Beclin-1和Bcl-2蛋白的表达情况,分析其与患者疾病进展及预后间的关系。结果: Beclin-1蛋白在癌旁组织中的高表达率显著高于NSCLC组织(49.2%比31.7%,P<0.01);而Bcl-2蛋白在NSCLC组织中的高表达率显著高于癌旁组织(45.8%比21.7%,P<0.01)。Beclin-1蛋白的表达情况与NSCLC的分化程度、病理分期及淋巴结转移有关,NSCLC患者的肿瘤分化程度越差、病理分期越高及存在淋巴结转移,Beclin-1蛋白的表达量也越低(P<0.05);Bcl-2蛋白的表达量则与NSCLC的肿瘤分化程度及淋巴结转移有关,肿瘤分化程度越差或存在肿瘤淋巴结转移,则Bcl-2蛋白的表达量越高(P<0.05)。Beclin-1和Bcl-2蛋白的表达与患者年龄、性别、吸烟、术前血清癌胚抗原(carcinoembryonic antigen,CEA)水平及肿瘤病理类型无关(P>0.05)。多因素 Cox风险比例回归分析结果显示,NSCLC的肿瘤细胞分化越差、病理分期越高及Beclin-1蛋白表达量越低可作为NSCLC患者预后差的独立标志物(P分别为<0.05、<0.01、<0.01)。NSCLC组织Bcl-2蛋白高表达组中,Beclin-1蛋白高表达者较低表达患者有更好的5年术后总生存率,差异有统计学意义(P<0.01)。结论: NSCLC患者肿瘤组织中自噬活性下降,Beclin-1蛋白低表达、Bcl-2蛋白高表达与NSCLC的发生及进展有关。高Beclin-1可作为Bcl-2蛋白高表达NSCLC患者的较好的独立预后标志物。
杜海磊, 陈聆, 罗方秀, 李勇, 程齐俭, 朱良纲, 杭钧彪 . Beclin-1和Bcl-2表达与非小细胞肺癌患者病理特征及预后间关系的研究[J]. 诊断学理论与实践, 2020 , 19(03) : 258 -263 . DOI: 10.16150/j.1671-2870.2020.03.010
Objective: To evaluate Beclin-1 and Bcl-2 in the prognosis of non-small cell lung cancer (NSCLC) by analyzing the expression of the two markers and clinical/pathological characteristics of patients. Methods: A total of 120 paired cancerous and paracancerous tissue samples from NSCLC patients were collected from surgical procedures and expressions of Belin-1 and Bcl-2 protein was determined with immunohistochemical analysis. The correlation between Belin-1 and Bcl-2 and the clinical/pathological characteristics of the patients was studied. Results: The high expression rate of Beclin-1 in the paracancerous tissues was significantly higher than that in the cancer tissues (49.2% vs 31.7%, P<0.01), while Bcl-2 in paracancerous tissues was significantly lower than that in cancer tissues (21.7% vs 45.8%, P<0.01). The lower expression of Beclin-1 in NSCLC was associated with poor differentiation, advanced pathological stage and lymph node metastasis(P<0.05). Higher Bcl-2 expression rate was correlated with poor differentiation and lymph node metastasis (P< 0.05). Neither Beclin-1 or Bcl-2 expression in lung cancer tissues was associated with age, gender, smoking, preope-rative serum CEA and tumor pathological type (P>0.05). Multivariate Cox regression analysis showed that advanced pathological stage, the lower the expression of Beclin-1,and poor differentiation were independent predictors of poor prognosis in patients with NSCLC (P<0.05, P<0.01, P<0.01). In patients with high expression of Bcl-2, high Beclin-1 expression was related to a better 5-year survival (P<0.01). Conclusions: The fuction of autophagy activity in NSCLC is decreased. Lower Beclin-1 expression and higher expression of Bcl-2 are found in NSCLC tissues, and both of them are associated with occurrence and progress of NSCLC. High Beclin-1 may serve as a favorable prognostic marker independently for NSCLC patients with high Bcl-2 expression.
Key words: Beclin-1; Bcl-2; Prognosis; Non-small cell lung cancer
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