组蛋白乙酰转移酶P300在肝癌组织中的表达及其临床意义

摘要/Abstract

摘要：

目的探讨组蛋白乙酰转移酶P300在肝癌中的表达及其临床意义。方法收集2013年1月至2017年12月四川绵阳四0四医院普外科收治的100例肝细胞癌患者的手术标本,检测肝癌组织中P300、CD90、甲胎蛋白(AFP)、Ki-67、CD34的表达。同时收集保存于医院实验室的42例肝脏血管瘤标本、56例有中重度肝硬化背景的肝组织标本,检测组织中P300的阳性表达率。分析P300表达与肝癌患者临床病理特征及预后的相关性。结果P300在正常肝组织、肝硬化组织、肝癌组织中的阳性表达率逐渐升高,分别为11.9%(5/42)、32.1%(18/56)、57.0%(57/100),差异具有统计学意义(χ²=27.192,P<0.001)。肿瘤分级(χ²=9.337,P=0.009)、T分期(χ²=8.794,P=0.032)、临床TNM分期(χ²=6.121,P=0.013)、AFP(χ²=11.040,P=0.001)、CD90(χ²=9.903,P=0.002)、CD34(χ²=4.066,P=0.044)对P300表达有明显影响。Spearman等级相关分析显示,P300的异常表达与AFP(r=0.335,P=0.001)、CD90(r=0.328,P=0.002)、CD34(r=0.264,P=0.047)的表达均呈正相关,但与Ki-67的表达无明显相关性(P>0.05)。生存分析发现,P300阳性表达患者的5年生存率为17.6%,阴性表达患者为62.5%,差异有统计学意义(χ²=10.596,P<0.001)。Cox多因素分析显示,P300阳性表达(RR=2.554,95%CI为1.261~4.502,P=0.009)、CD90阳性表达(RR=3.574,95%CI为1.021~11.980,P=0.030)和TNM Ⅱ~Ⅳ期(RR=0.332,95%CI为0.105~0.596,P=0.002)是肝癌患者预后不良的独立危险因素。结论P300阳性表达与肝癌的发生密切相关,可作为判断肝癌患者预后不良的独立性因素。

关键词:肝肿瘤,预后,组蛋白乙酰转移酶P300

Abstract:

ObjectiveTo investigate the expression and clinical significance of histone acetyltransferase P300 in hepatocellular carcinoma.MethodsFrom January 2013 to December 2017, surgical specimens of 100 patients with hepatocellular carcinoma were collected from the Department of General Surgery of Sichuan Mianyang 404 Hospital. The expressions of P300, CD90, alpha fetoprotein (AFP), Ki-67 and CD34 in hepatocellular carcinoma tissue were detected. At the same time, 42 hepatic hemangioma specimens and 56 liver tissue specimens with moderate to severe liver cirrhosis were collected, and the positive expression rate of P300 in tissues was detected. The correlations between the expression of P300 and clinicopathological features and prognosis of patients with hepatocellular carcinoma were analyzed.ResultsThe positive expression rates of P300 in normal liver tissue, liver cirrhosis tissue and hepatocellular carcinoma tissue increased gradually, which were 11.9% (5/42), 32.1% (18/56) and 57.0% (57/100) respectively, with a statistically significant difference (χ²=27.192,P<0.001). Tumor grade (χ²=9.337,P=0.009), T stage (χ²=8.794,P=0.032), clinical TNM stage (χ²=6.121,P=0.013), AFP (χ²=11.040,P=0.001), CD90 (χ²=9.903,P=0.002), CD34 (χ²=4.066,P=0.044) significantly affected the expression of P300. Spearman rank correlation analysis showed that the abnormal expression of P300 was positively correlated with the expression of AFP (r=0.335,P=0.001), CD90 (r=0.328,P=0.002) and CD34 (r=0.264,P=0.047), but had no significant correlation with the expression of Ki-67 (P>0.05). Survival analysis showed that the 5-year survival rate of patients with P300 positive expression was 17.6%, and that of patients with P300 negative expression was 62.5%, and there was a statistically significant difference (χ²=10.596,P<0.001). Cox multivariate analysis showed that P300 positive expression (RR=2.554, 95%CI: 1.261-4.502,P=0.009), CD90 positive expression (RR=3.574, 95%CI: 1.021-11.980,P=0.030) and TNM Ⅱ-Ⅳ stage (RR=0.332, 95%CI: 0.105-0.596,P=0.002) were independent risk factors for poor prognosis of patients with hepatocellular carcinoma.ConclusionThe positive expression of P300 is closely related to the occurrence of hepatocellular carcinoma and can be used as an independent factor to judge the poor prognosis of patients with hepatocellular carcinoma.

Key words:Liver neoplasms,Prognosis,Histone acetyltransferase P300

韩保俊. 组蛋白乙酰转移酶P300在肝癌组织中的表达及其临床意义[J]. 国际肿瘤学杂志, 2021, 48(7): 415-419.

Han Baojun. Expression of histone acetyltransferase P300 in hepatocellular carcinoma tissue and its clinical significance[J]. Journal of International Oncology, 2021, 48(7): 415-419.

图/表5

图1

表1

100例肝癌患者P300表达与临床病理特征的关系(例)"

临床病理特征	P300阴性 (n=43)	P300阳性 (n=57)	χ²值	P值	临床病理特征	P300阴性 (n=43)	P300阳性 (n=57)	χ²值	P值
性别					TNM分期
男	28	35	0.145	0.703	Ⅰ	25	19	6.121	0.013
女	15	22			Ⅱ~Ⅳ	18	38
肿瘤病理分级					AFP
1	5	2			阴性	31	22	11.040	0.001
2	29	27	9.337	0.009	阳性	12	35
3	9	28			CD90
肿瘤直径(cm)					阴性	22	12	9.903	0.002
<10	34	35	3.576	0.059	阳性	21	45
≥10	9	22			CD34
T分期					阴性	17	12	4.066	0.044
T₁	12	5			阳性	26	45
T₂	13	19	8.794	0.032	Ki-67
T₃	18	29			阴性	28	27	3.119	0.077
T₄	0	4			阳性	15	30
N分期
N₀	42	54	0.551	0.458
N₁	1	3

表1

表2

肝癌组织中P300与CD90、AFP、Ki-67、CD34表达的相关性(例)"

肿瘤标志物	P300表达		r值	P值
肿瘤标志物	阴性	阳性	r值	P值
AFP
阴性	31	22	0.335	0.001
阳性	12	35
CD90
阴性	22	12	0.328	0.002
阳性	21	45
CD34
阴性	17	12	0.264	0.047
阳性	26	45
Ki-67
阴性	28	27	0.178	0.082
阳性	15	30

表2

图2

指标	β值	SE值	Wald值	RR值	95%CI	P值
P300表达(阳性/阴性)	0.869	0.326	7.133	2.554	1.261~4.502	0.009
CD90表达(阳性/阴性)	1.273	0.586	4.745	3.574	1.021~11.980	0.030
AFP表达(阳性/阴性)	0.260	0.268	1.112	1.310	0.769~1.898	0.300
Ki-67表达(阳性/阴性)	0.176	0.317	0.290	1.180	0.645~2.179	0.633
肿瘤分级(1~2级/3级)	-0.599	0.350	2.939	0.549	0.277~1.090	0.086
TNM分期(Ⅰ期/Ⅱ~Ⅳ期)	-1.570	0.188	77.635	0.332	0.105~0.596	0.002
T分期(T_1-2期/T_3-4期)	-0.454	0.282	2.597	0.639	0.368~1.125	0.107

表3

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