缺氧诱导因子1α在乳头状肾细胞癌中的表达及其与预后的关系

doi:10.16150/j.1671-2870.2021.03.007

摘要/Abstract

摘要：

目的:检测缺氧诱导因子1α（hypoxia-inducible factor-1ɑ,HIF-1α）在乳头状肾细胞癌（papillary renal cell carcinoma, PRCC）组织中的表达情况,分析其与微血管密度（microvessel density, MVD）间的关系,并探讨HIF-1α与患者预后间的关系。方法:应用免疫组织化学（免疫组化）技术检测PRCC组织和癌旁肾组织（对照）中HIF-1α及MVD表达,分析二者之间的相关性。采用Kaplan-Meier法和Logrank法对患者的生存数据进行分析,对有意义的因素行Cox模型多因素回归分析。结果:PRCC组织中HIF-1α的阳性表达率为42.17%（35/83）,其中Ⅰ型、Ⅱ型PRCC组织中HIF-1α阳性表达率分别为32.65%、55.88%,二者间差异有统计学意义（P=0.035）。Ⅱ型PRCC组织中的MVD高于Ⅰ型PRCC（40.74个/高倍镜比25.63个/高倍镜）,在Ⅰ型和Ⅱ型PRCC中,HIF-1α的表达均与MVD呈正相关（γ=0.65）。83例PRCC患者的5年生存率为89.16%（74/83）,13例死亡的病例中,10例为Ⅱ型PRCC,采用Kaplan-Meier生存曲线分析显示,Ⅰ型PRCC患者的预后好于Ⅱ型PRCC（5年总体生存率87.8%比76.5%, P<0.05）。单因素分析显示,肾细胞癌Fuhrman核分级Ⅲ~Ⅳ级、肿瘤发生远处转移和HIF-1α阳性表达是PRCC患者预后不良的危险因素;多因素分析显示,Ⅱ型PRCC、Fuhrman核分级Ⅲ~Ⅳ级、肿瘤远处转移及HIF-1α阳性表达是PRCC预后不良的因素。结论:相对于Ⅰ型PRCC,HIF-1α在Ⅱ型PRCC组织中的阳性率更高,其阳性表达是PRCC患者预后不良的因素。

关键词: 乳头状肾细胞癌, 缺氧诱导因子1ɑ, 微血管密度, 预后

Abstract:

Objects: To investigate the expression of hypoxia inducible factor-1ɑ（HIF-1ɑ） in papillary renal cell carcinoma (PRCC) and its relationship with microvessel density so as to explore the correlation of HIF-1ɑ expression with prognosis in PRCC patients. Methods: Immunohistochemistry was used to detect the expression of HIF-1ɑ in PRCC and para-carcinoma tissue and the relationship between expression of HIF-1ɑ and MVD was analyzed. Survival data were eva-luated with Kaplan-Meier and Log-rank method, and the significant factors were further analyzed with Cox model multivariate regression analysis. Results: The positive expression rate of HIF-1ɑ was 42.17% (35/83), and the positive expression rates in typeⅠand type II PRCC were 32.65% and 55.88%, respectively. The MVD in typeⅡPRCC was higher than that in typeⅠPRCC (40.74 /HP vs 25.63/HP), and HIF-1ɑ expression was positively correlated with MVD (γ=0.65). The 5-year survival rate of 83 PRCC patients was 89.16% (74/83), and of the 13 death cases, 10 cases were type Ⅱ PRCC. The Kaplan-Meier survival curve analysis showed that typeⅠPRCC had a better prognosis than typeⅡ. Univariate analysis revealed that Fuhrman grade Ⅲ-Ⅳ, occurrence of distant metastasis and HIF-1ɑ expression were risk factors for prognosis in PRCC patients (P<0.05). Multivariate analysis showed that HIF-1ɑ expression, Fuhrman grade, subtype of PRCC and distant metastasis were risk factors for poor prognosis. Conclusions: HIF-1ɑ expression is higher in typeⅡPRCC than in typeⅠPRCC, and HIF-1ɑ expression is a risk factor for poor prognosis in PRCC patients.

Key words: Papillary renal cell carcinoma, Hypoxia inducible factor-1α, Microvessel density, Prognosis

中图分类号:

R737.1

芮文斌, 徐达, 祝宇, 吴瑜璇, 王浩飞, 汪成合, 袁菲. 缺氧诱导因子1α在乳头状肾细胞癌中的表达及其与预后的关系[J]. 诊断学理论与实践, 2021, 20(03): 265-370.

RUI Wenbin, XU Da, ZHU Yu, WU Yuxuan, WANG Haofei, WANG Chenghe, YUAN Fei. Expression of HIF-1α and its relationship with prognosis in papillary renal cell carcinoma[J]. Journal of Diagnostics Concepts & Practice, 2021, 20(03): 265-370.

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组别	例数(n)	MVD（个/高倍镜）	Z值	P值
Ⅰ型PRCC	49	28.61±9.39	0.007^a)	-2.70^a)
Ⅱ型PRCC	34	36.88±13.59	0.001^a)	-3.30^a)
正常肾组织	15	14.07±5.95

组别	例数(n)	MVD（个/高倍镜）	r值	P值
HIF-1α阳性组	35	25.63±5.44
HIF-1α阴性组	48	40.74±12.92	0.63	<0.001

变量	单因素分析		Cox回归
变量	r	P值	r	P值
性别	-0.22	0.98	0.04	0.910
年龄	0.01	0.99	0.01	0.450
体重	-0.22	0.55	0.11	0.500
亚型	11.74	0.06	-0.78	<0.001
Fuhrman分级（Ⅰ+Ⅱ比Ⅲ+Ⅳ）	-23.57	<0.01	0.76	0.020
T分期(T_1~2比T_3~4)	-7.14	0.28	0.16	0.590
N分期(N₀比N₁)	-16.53	0.19	-0.41	0.600
M分期(M₀比M₁)	-36.60	0.03	1.00	<0.001
HIF-1α	-29.38	<0.01	1.18	0.001