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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
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。
Expression and clinical significance of forkhead box A2 and forkhead box J2 in hepatocellular carcinoma
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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(rs=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。 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 (rs=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. -
Key words:
- Carcinoma, Hepatocellular /
- Forkhead Transcription Factors /
- Prognosis
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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。
图 1 FOXA2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。
图 2 FOXJ2在HCC组织中的表达水平(免疫组化S-P法，×400)
表 1 FOXA2、FOXJ2表达的半定量分析
项目 FOXA2 FOXJ2 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 
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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 阴性(n=16) 阳性(n=38) 阴性(n=13) 阳性(n=41) 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
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