叉头转录因子A2、J2在肝细胞癌组织中的表达及意义

冉小柯; 陈欣菊; 赵云霞; 张鑫; 杨荷; 孙祎尧; 陈晓琦

doi:10.3969/j.issn.1001-5256.2021.06.025

叉头转录因子A2、J2在肝细胞癌组织中的表达及意义

DOI: 10.3969/j.issn.1001-5256.2021.06.025

1.
河南中医药大学第一临床医学院，郑州 450046
2.
河南中医药大学第一附属医院消化科，郑州 450000

基金项目:

国家科技重大专项-艾滋病和病毒性肝炎等重大传染病防治项目 (2018ZX10303502-001);

河南省中医药科学研究专项课题重点项目 (2018JDZX110);

河南省中医药科学研究专项课题 (2017JDZX029);

河南省特色骨干学科中医学学科建设项目 (STG-ZYXKY-2020019)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：冉小柯负责课题设计，资料分析，撰写论文；赵云霞、张鑫、杨荷、孙祎尧参与收集数据，修改论文；陈晓琦、陈欣菊负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

作者简介:
冉小柯(1997—)，女，主要从事中西医结合防治消化疾病方面的研究

通信作者:
陈晓琦，28050827@qq.com

中图分类号: R735.7
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- 被引次数: 0
出版历程
- 收稿日期: 2020-10-18
- 录用日期: 2020-12-25
- 出版日期: 2021-06-20

Expression and clinical significance of forkhead box A2 and forkhead box J2 in hepatocellular carcinoma

1.
The First Clinical Medical College of Henan University of Traditional Chinese Medicine, Zhengzhou 450046, China
2.
Department of Gastroenterology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China

摘要

摘要: 目的检测肝细胞癌(HCC)组织中叉头(FOX)转录因子A2(FOXA2)与FOXJ2的表达水平，探讨FOXA2、FOXJ2与HCC的相关性。方法选取2014年1月—2019年7月于河南中医药大学第一附属医院病理学检查明确为HCC患者54例，收集临床资料和病理组织。采用免疫组化S-P法检测HCC组织中FOXA2与FOXJ2的蛋白水平表达，分析其与HCC相关临床病理特征及患者预后的关系。计数资料比较采用χ²检验与校正χ²检验，FOXJ2与FOXA2表达相关性采用Spearman相关分析法；采用Kaplan-Merier法进行生存期分析；采用Image-Pro Plus进行FOXA2、FOXJ2表达的半定量分析；采用Wilcoxon秩和检验比较组间差异。结果 HCC组织中FOXA2和FOXJ2蛋白表达阳性率分别为70.37%(38/54)和75.92%(41/54)；FOXA2和FOXJ2表达水平间呈显著正相关(r_s=0.648，P＜0.001)。FOXA2阴性组与阳性组相比，肿瘤直径、分化程度、肿瘤个数、AFP水平差异均有统计学意义(χ²值分别为5.440、4.113、4.352、3.865，P值分别为0.020、0.043、0.037、0.049)；FOXJ2阴性组与阳性组比较，分化程度差异有统计学意义(χ²=9.267，P=0.002)。FOXA2、FOXJ2阳性表达组HCC患者的累积生存率均显著高于FOXA2、FOXJ2阴性表达组HCC患者(P值均＜0.01)。结论 FOXA2与FOXJ2的表达水平可能与HCC的发生发展及预后相关，二者在HCC的发生发展中起协同作用。
- 癌，肝细胞 /
- 叉头转录因子类 /
- 预后
Abstract: Objective To investigate the expression levels of forkhead box A2 (FOXA2) and forkhead box J2 (FOXJ2) in hepatocellular carcinoma (HCC) tissue and the association of FOXA2 and FOXJ2 with HCC. Methods Clinical data and pathological tissue samples were collected from 54 patients with pathologically confirmed HCC in The First Affiliated Hospital of Henan University of Traditional Chinese Medicine from January 2014 to July 2019. The immunohistochemical SP method was used to measure the protein expression levels of FOXA2 and FOXJ2 in HCC tissue, and their association with HCC-related clinicopathological features and patient prognosis was analyzed. The chi-square test and the adjusted chi-square test were used for comparison of categorical data; a Spearman correlation analysis was performed to investigate the correlation between the expression of FOXA2 and FOXJ2; the Kaplan-Meier method was used for survival analysis; Image-Pro Plus was used to perform the semi-quantitative analysis of the expression of FOXA2 and FOXJ2; the Wilcoxon rank-sum test was used for comparison between groups. Results The positive rates of the protein expression of FOXA2 and FOXJ2 in HCC tissue were 70.37% (38/54) and 75.92% (41/54), respectively, and there was a significant positive correlation between the expression levels of FOXA2 and FOXJ2 (r_s=0.648, P < 0.001). In both negative and positive groups, the expression level of FOXA2 was associated with tumor diameter, degree of tumor differentiation, number of tumors, and alpha-fetoprotein (χ²=5.440, 4.113, 4.352, and 3.865, P=0.020, 0.043, 0.037, and 0.049), and the expression level of FOXJ2 was associated with the degree of tumor differentiation (χ²=9.267, P=0.002). The group with positive expression of FOXA2 and FOXJ2 had a significantly higher cumulative survival rate than the group with negative expression of FOXA2 and FOXJ2 (P < 0.01). Conclusion The expression levels of FOXA2 and FOXJ2 are associated with the development, progression, and prognosis of HCC, and they have a synergistic effect in the development and progression of HCC.
- Carcinoma, Hepatocellular /
- Forkhead Transcription Factors /
- Prognosis

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图 1 FOXA2在HCC组织中的表达水平(免疫组化S-P法，×400)

注：a, FOXA2在HCC组织中不表达；b, FOXA2在HCC组织中低表达；c, FOXA2在HCC组织中中度表达；d, FOXA2在HCC组织中高表达。

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图 2 FOXJ2在HCC组织中的表达水平(免疫组化S-P法，×400)

注：a, FOXJ2在HCC组织中不表达；b, FOXJ2在HCC组织中低表达；c, FOXJ2在HCC组织中中度表达；d, FOXJ2在HCC组织中高表达。

下载: 全尺寸图片幻灯片

图 3 FOXA2阳性表达及阴性表达HCC患者的生存曲线

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图 4 FOXJ2阳性表达及阴性表达HCC患者的生存曲线

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表 1 FOXA2、FOXJ2表达的半定量分析

项目	FOXA2		FOXJ2
项目	Area	IOD	Area	IOD
不表达	24.60±13.35	3.51±1.91	24.60±13.35	2.96±1.63
低表达	204.53±147.05	84.15±70.3	175.46±537.81	13.14±110.56
中度表达	310.03±214.34	89.02±69.06	400.69±1 551.80	180.63±695.20
高表达	577.11±1212.88	445.26±939.64	1 505.42±9 001.71	652.10±3 987.02

下载: 导出CSV

表 2 FOXA2、FOXJ2的表达与肝癌相关临床病理特征的关系

项目	例数	FOXA2		χ²值	P值	FOXJ2		χ²值	P值
项目	例数	阴性(n=16)	阳性(n=38)	χ²值	P值	阴性(n=13)	阳性(n=41)	χ²值	P值
性别(例)				0	1.000			0.006	0.940
男	44	13	31			10	34
女	10	3	7			3	7
年龄(例)				0.558	0.455			0.001	0.971
＜60岁	33	11	22			8	25
≥60岁	21	5	16			5	16
肿瘤直径(例)				5.440	0.020			2.026	0.155
≤5 cm	30	5	25			5	25
＞5 cm	24	11	13			8	16
分化程度(例)				4.113	0.043			9.267	0.002
低/中分化	11	6	5			7	4
高分化	43	10	33			6	37
TNM分期(例)				0.032	0.859			0.453	0.501
Ⅰ~Ⅱ期	43	12	31			9	34
Ⅲ~Ⅳ期	11	4	7			4	7
门静脉癌栓(例)				1.072	0.300			2.612	0.106
有	12	5	7			5	7
无	42	11	31			8	34
转移(例)				0.012	0.913			0	1.000
有	8	3	5			2	6
无	46	13	33			11	35
肿瘤个数(例)				4.352	0.037			1.621	0.203
单个	27	4	23			4	23
多个	27	12	15			9	18
AFP(例)				3.865	0.049			2.038	0.153
≤20 ng/ml	28	5	23			4	24
＞20 ng/ml	26	11	15			9	17

下载: 导出CSV

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