Gli基因及蛋白在肝细胞癌组织中的表达及与预后的关系

doi:10.11958/20240977

天津医药 ›› 2025, Vol. 53 ›› Issue (2): 124-128.doi: 10.11958/20240977

Gli基因及蛋白在肝细胞癌组织中的表达及与预后的关系

俞松松(), 尹京兆, 吴天俣, 李浩()

延边大学附属医院（延边医院）肝胆胰外科（邮编133000）

收稿日期:2024-07-21 修回日期:2024-12-12 出版日期:2025-02-15 发布日期:2025-02-26
通讯作者: ^△ E-mail：lih@ybu.edu.cn
作者简介:俞松松（1997），男，硕士在读，主要从事肝胆胰脾疾病的研究。E-mail：yssyyyyy@163.com
基金资助:
吉林省卫生健康科技能力提升项目(2021jc065)

Gli gene and protein expression in hepatocellular carcinoma and the relationship with prognosis

YU Songsong(), YIN Jingzhao, WU Tianyu, LI Hao()

Department of Hepatopancreatobiliary Surgery, Yanbian University Hospital, Yanji 133000, China

Received:2024-07-21 Revised:2024-12-12 Published:2025-02-15 Online:2025-02-26
Contact: ^△ E-mail：lih@ybu.edu.cn

俞松松, 尹京兆, 吴天俣, 李浩. Gli基因及蛋白在肝细胞癌组织中的表达及与预后的关系[J]. 天津医药, 2025, 53(2): 124-128.

YU Songsong, YIN Jingzhao, WU Tianyu, LI Hao. Gli gene and protein expression in hepatocellular carcinoma and the relationship with prognosis[J]. Tianjin Medical Journal, 2025, 53(2): 124-128.

摘要/Abstract

摘要：

目的探讨Gli1、Gli2和Gli3基因及蛋白在肝细胞癌（HCC）组织中的表达特征及其与预后的关系。方法利用cBioportal数据库分析315例HCC样本中Gli基因的表达情况，并通过免疫组织化学方法检测40例HCC及其他肝脏组织中Gli蛋白的表达水平。结果 315例HCC样本中57例（18.1%）出现Gli基因改变，Gli1、Gli2和Gli3的改变频率分别为19例（6.0%）、13例（4.1%）和25例（7.9%）。Gli1与Gli2，Gli1与Gli3呈现显著共存性（P<0.05），而Gli2与Gli3表现出互斥趋势。Gli1基因表达增加的患者无病生存率明显降低（P<0.01）。免疫组织化学结果显示，Gli1蛋白在HCC组织中的表达显著高于正常肝脏、癌旁组织、病毒性肝炎和肝硬化/肝纤维化组织（P<0.05）。在HCC组织中，Gli蛋白间呈现出较强的正相关性（Gli1 vs. Gli2：r_s=0.796；Gli1 vs. Gli3：r_s=0.759；Gli2 vs. Gli3 r_s=0.891，均P<0.01）。53.3%（8/15）的HCC样本同时呈现3种Gli蛋白的高表达，而在非癌肝组织中仅为11.8%（2/17）。结论 Gli1、Gli2和Gli3蛋白在HCC组织中普遍呈现协同高表达和显著正相关，Gli1出现独立高表达的特殊表达模式。

关键词: 肝肿瘤, 转录因子, 基因表达, Gli, cBioportal基因数据库

Abstract:

Objective To investigate the expression patterns of Gli1, Gli2 and Gli3 genes and proteins in hepatocellular carcinoma (HCC) tissue and their correlation with prognosis. Methods Gli gene expression in 315 HCC samples were analyzed using the cBioportal database, and Gli protein expression was examined in 40 HCC and other liver tissue samples through immunohistochemistry. Results Gli gene alterations were found in 57 cases (18.1%) of HCC samples, with alteration frequencies of 19 cases (6.0%), 13 cases (4.1%) and 25 cases (7.9%) for Gli1, Gli2 and Gli3, respectively. Gli1 showed significant co-occurrence with both Gli2 and Gli3 (P<0.05), while Gli2 and Gli3 exhibited a tendency toward mutual exclusivity. Increased Gli1 gene expression significantly correlated with decreased disease-free survival (P<0.01). Immunohistochemical analysis demonstrated that Gli1 protein expression was significantly higher in HCC tissue than that in normal liver tissue, adjacent tissue, hepatitis and cirrhotic tissue (P<0.05). In HCC tissue, strong positive correlation was observed between the three Gli proteins (Gli1 vs. Gli2: r_s=0.796; Gli1 vs. Gli3: r_s=0.759; Gli2 vs. Gli3:r_s=0.891, all P<0.01). High expression levels of all three Gli proteins were detected in 53.3% (8/15) of HCC samples, compared to only 11.8% (2/17) in non-cancerous liver tissue. Conclusion Gli1, Gli2 and Gli3 proteins commonly exhibit synergistic high expression and significant positive correlation in HCC tissue, with Gli1 showing a special expression pattern of independent high expression.

Key words: liver neoplasms, transcription factors, gene expression, Gli, cBioportal gene database

中图分类号:

R735.7

图/表 6

图1 HCC中Gli1、Gli2、Gli3基因的表达变化

Fig.1 Alterations in the expression levels of Gli1, Gli2 and Gli3 genes in hepatocellular carcinoma

表1 3种Gli基因改变互斥性和共存性比较

Tab.1 Comparison of exclusivity and coexistence between three types of Gli gene

基因A	基因B	共同改变	只有A改变	只有B改变	均无改变	$L o g 2 O R$	P	趋势
Gli1	Gli3	7	15	21	305	2.761	<0.001	共存
Gli1	Gli2	3	19	10	316	2.319	0.042	共存
Gli2	Gli3	0	13	28	307	<-3.000	0.329	互斥

表1 3种Gli基因改变互斥性和共存性比较

Tab.1 Comparison of exclusivity and coexistence between three types of Gli gene

基因A	基因B	共同改变	只有A改变	只有B改变	均无改变	$L o g 2 O R$	P	趋势
Gli1	Gli3	7	15	21	305	2.761	<0.001	共存
Gli1	Gli2	3	19	10	316	2.319	0.042	共存
Gli2	Gli3	0	13	28	307	<-3.000	0.329	互斥

图2 Gli基因改变对HCC癌患者总体生存率和无病生存率的影响

Fig.2 Correlation between Gli gene alterations and overall survival as well as disease-free survival in hepatocellular carcinoma

图3 Gli1、Gli2、Gli3蛋白在正常以及肝细胞癌组织中的表达（×200）

Fig.3 Expression of Gli1, Gli2 and Gli3 proteins in normal tissue and hepatocellular carcinoma tissue (×200)

表2 正常及疾病肝脏组织中的Gli1、Gli2、Gli3表达情况比较 [M（P25，P75）]

Tab.2 Comparison of Gli1, Gli2 and Gli3 expression between normal tissue and diseased liver tissue

组织类型	n	Gli1	Gli2	Gli3
正常肝脏	2	0.00（0.00，0.01）	0.06（0.05，0.07）	0.02（0.01，0.02）
癌旁组织	2	0.01（0.00，0.02）	0.13（0.08，0.16）	0.05（0.04，0.07）
病毒性肝炎	5	0.02（0.00，0.05）	0.12（0.09，0.16）	0.06（0.03，0.07）
肝硬化/ 肝纤维化	8	0.05（0.02，0.09）	0.11（0.06，0.19）	0.05（0.02，0.07）
HCC	15	0.21（0.06，0.50）^abcd	0.09（0.04，0.20）^a	0.06（0.02，0.09）^a
H		25.370^＊＊	9.820^＊	11.730^＊

图4 正常及疾病肝脏组织中每个样本Gli1、Gli2、Gli3蛋白共同表达模式图中每个点代表1个样本。

Fig.4 Co-expression patterns of Gli1, Gli2 and Gli3 proteins in each sample of normal tissue and diseased liver tissue

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Gli基因及蛋白在肝细胞癌组织中的表达及与预后的关系

Gli gene and protein expression in hepatocellular carcinoma and the relationship with prognosis

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