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

doi:10.16150/j.1671-2870.2020.03.010

摘要/Abstract

摘要：

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。

关键词: Beclin-1, Bcl-2, 预后, 非小细胞肺癌

Abstract:

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

中图分类号:

R734.2

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.

DU Hailei, CHEN Ling, LUO Fangxiu, LI Yong, CHENG Qijian, ZHU Lianggang, HANG Junbiao. The prognostic value of Beclin-1 and Bcl-2 and its relationship with pathological characteristics in patients with non-small cell lung cancer[J]. Journal of Diagnostics Concepts & Practice, 2020, 19(03): 258-263.

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临床参数	例数（n=120)	Beclin-1表达		χ²值	P值
临床参数	例数（n=120)	高表达（n=38)	低表达（n=82)	χ²值	P值
性别
男性	56(46.67)	16(13.33)	40(33.33)	0.46	>0.05
女性	64(53.33)	22(18.33)	42(35.00)
吸烟史
是	54(45.00)	13(10.83)	41(34.17)	2.62	>0.05
否	66(55.00)	25(20.83)	41(34.17)
年龄（岁）
≤60	41(34.17)	16(13.34)	25(20.83)	1.56	>0.05
>60	79(65.83)	22(18.33)	57(47.50)
病理分期				6.54	<0.05
Ⅰ	59(49.17)	25(20.83)	34(28.33)
Ⅱ	42(35.00)	10(8.33)	32(26.67)
Ⅲ	19(15.83)	3(2.50)	16(13.33)
淋巴结转移				4.53	<0.05
有	45(37.50)	9(7.50)	36(30.00)
无	75(62.50)	29(24.17)	46(38.33)
病理类型				0.89	>0.05
腺癌	83(69.17)	28(23.33)	55(45.83)
鳞癌	31(25.83)	9(7.50)	22(18.33)
其他	6(5.00)	1(0.83)	5(4.17)
分化程度				6.90	<0.05
高分化	25(20.83)	12(10.00)	13(10.83)
中分化	62(51.67)	21(17.5)	41(34.17)
低分化	33(27.50)	5(4.17)	28(23.33)
CEA（术前）				1.99	>0.05
≤5 μg/L	55(45.83)	21(17.5)	34(28.33)
>5 μg/L	65(54.17)	17(14.17)	48(40.00)

临床参数	例数（n）	Bcl-2表达		χ²值	P值
临床参数	例数（n）	高表达	低表达	χ²值	P值
性别	120	55	65
男性	56(46.67%)	24(20.00%)	32(26.67%)	0.37	>0.05
女性	64(53.33%)	31(25.83%)	33(27.50%)
吸烟史
是	54(45.00%)	23(19.17%)	31(25.83%)	0.42	>0.05
否	66(55.00%)	32(26.67%)	34(28.33%)
年龄（岁）
≤60	41(34.17%)	16(13.33%)	25(20.84%)	1.16	>0.05
>60	79(65.83%)	39(32.50%)	40(33.33%)
病理分期				0.02	>0.05
Ⅰ	59(49.17%)	27(22.50%)	32(26.67%)
Ⅱ	42(35.00%)	19(15.83%)	23(19.17%)
Ⅲ	19(15.83%)	9(7.50%)	10(8.33%)
淋巴结转移				4.14	<0.05
有	45(37.50%)	26(21.67%)	19(15.83%)
无	75(62.50%)	29(24.17%)	46(38.33%)
病理类型				2.70	>0.05
腺癌	83(69.17%)	34(28.33%)	49(40.84%)
鳞癌	31(25.83%)	18(15.00%)	13(10.83%)
其他	6(5.00%)	3(2.50%)	3(2.50%)
分化程度				6.87	<0.05
高分化	25(20.83%)	7(5.83%)	18(15.00%)
中分化	62(51.67%)	34(28.33%)	28(23.34%)
低分化	33(27.50%)	20(16.67%)	13(10.83%)
CEA（术前）				0.43	>0.05
≤5 μg/L	55(45.83%)	27(22.50%)	28(23.33%)
>5 μg/L	65(54.17%)	28(23.33%)	37(30.84%)

临床参数	死亡	P值
临床参数	风险比 (95% CI)	P值
性别（男比女）	2.977(0.612~14.492)	0.177
年龄（≤60比>60）	1.132（0.534~3.221）	0.554
吸烟（是比否）	0.421（0.093~1.910）	0.262
病理分期（Ⅰ比Ⅱ比Ⅲ）	10.844（3.885~30.265）	<0.010
淋巴结转移（是比否）	0.964（0.295~3.156）	0.952
病理类型（腺癌比鳞癌比其他）	1.221（0.627~2.380）	0.557
肿瘤分化（高比中比低）	2.819（1.425~5.575）	<0.010
CEA (μg/L)（≤5比>5）	5.678（1.035~31.156）	0.046
Beclin-1（高表达比低表达）	5.319（1.844~15.348）	<0.010
Bcl-2（高表达比低表达）	0.436（0.166~1.144）	0.092

临床参数	死亡	P值
临床参数	风险比 (95% CI)	P值
病理分期（Ⅰ比Ⅱ比Ⅲ）	13.707(5.553~33.863)	<0.01
肿瘤分化（高比中比低）	2.114（1.185~3.770）	<0.05
CEA (μg/L)（≤5比>5）	4.373（0.958~19.954）	>0.05
Beclin-1（高表达比低表达）	4.508（1.753~11.591）	<0.01