EXO1在肝细胞癌中的预后和免疫意义的综合分析

于金慧; 王威; 吕振宇; 季文斌; 余晖豪; 杨燕

doi:10.16766/j.cnki.issn.1674-4152.003742

EXO1在肝细胞癌中的预后和免疫意义的综合分析

doi: 10.16766/j.cnki.issn.1674-4152.003742

蚌埠医科大学第一附属医院肿瘤内科，安徽蚌埠 233004

基金项目:

安徽省教育厅高校自然科学研究重大项目 2023AH040291

安徽省高校优秀青年人才支持计划项目 gxyq2022042

蚌埠医科大学研究生科研创新计划项目 Byycx23058

详细信息

通讯作者:
杨燕，E-mail：qiannianhupo@163.com

中图分类号: R735.7 R730.5
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- 文章访问数: 31
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- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2024-05-11
- 网络出版日期: 2024-12-31

Comprehensive analysis of the prognostic and immunological significance of EXO1 in hepatocellular carcinoma

Department of Medical Oncology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233004, China

摘要

摘要: 目的分析外切核酸酶1(EXO1)在肝细胞癌(HCC)中的表达，探究EXO1与HCC患者预后及免疫细胞浸润的关系。方法 TCGA、GEO数据库分析EXO1在HCC与正常组织中的表达，qRT-PCR揭示EXO1在HCC细胞系中的表达。采用logistic回归分析研究EXO1表达与临床病理特征的关系；利用Kaplan-Meier分析、Cox回归分析研究EXO1表达与患者预后的关系；利用GSVA中单样本GSEA(ssGSEA)算法和TIMER数据库进行免疫浸润分析。结果 HCC中EXO1 mRNA表达高于正常肝组织(P＜0.001)；与正常肝细胞系LO2相比，EXO1 mRNA在HCC细胞系BEL-7404和SMMC-7721中表达上调(3.92±0.75，2.42±0.52 vs.1.00±0.00；P＜0.05)；EXO1表达水平与肿瘤T分期、组织学分级、病理学分期均相关(P＜0.001)；EXO1高表达与HCC患者较差的总生存期相关(P＜0.001)；免疫浸润分析示，EXO1表达与多种免疫细胞浸润有关。结论高表达EXO1与HCC患者不良预后及免疫细胞浸润显著相关，可能成为HCC患者一个潜在的预后生物标志物及免疫干预靶点。
- 肝细胞癌 /
- 外切核酸酶1 /
- 生物标志物 /
- 预后 /
- 免疫浸润
Abstract: Objective To analyze the expression of exonuclease 1 (EXO1) in hepatocellular carcinoma (HCC) and to investigate the relationship between EXO1 and prognosis and immune cell infiltration in patients with HCC. Methods The expression of EXO1 in HCC and normal tissues was analyzed based on The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, Furthermore, EXO1 mRNA expression was verified in HCC cell lines by qRT-PCR analysis. The correlation between EXO1 expression and clinicopathological features was analyzed using logistic regression. Kaplan-Meier analysis and Cox regression were used to determine the correlation between EXO1 expression and patients prognosis. The GSVA ssGSEA algorithm and the TIMER database were employed to examine the correlation between EXO1 expression and the level of immune infiltration. Results The expression of EXO1 mRNA in HCC tissues was found to be significantly higher than that in normal tissues (P < 0.001). Furthermore, the EXO1 mRNA level in HCC cell lines, BEL-7404 and SMMC-7721 was observed to be markedly elevated in comparison to that in a normal hepatic cell line LO2 (3.92±0.75, 2.42±0.52 vs. 1.00±0.00; P < 0.05). There was a significant correlation between EXO1 expression and the T stage, histological grade and pathological stage of tumors (P < 0.001). A high level of EXO1 expression was found to be associated with poorer overall survival rate in HCC patients (P < 0.001). The analysis of immune infiltration revealed a correlation between EXO1 expression and the infiltration of multiple immune cells. Conclusion High EXO1 expression is associated with an unfavourable prognosis and immune cell infiltration in HCC patients. This may serve as a potential prognostic biomarker and immune intervention target in HCC.
- Hepatocellular carcinoma /
- Exonuclease 1 /
- Biomarker /
- Prognosis /
- Immune infiltration

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图 1 EXO1 mRNA在公共数据库中的表达情况

注：^aP＜0.05。

Figure 1. Expression level of EXO1-mRNA in public databases

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图 2 EXO1对HCC患者预后的预测价值分析

注：A为不同EXO1表达水平组HCC患者的生存曲线；B为EXO1预测HCC患者1年、3年及5年OS的ROC曲线。

Figure 2. Analysis of EXO1 as a prognostic predictor for HCC patients

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图 3 免疫细胞浸润水平对HCC患者预后的影响

注：A为中性粒细胞水平与HCC患者预后的关系; B为M0巨噬细胞水平与HCC患者预后的关系; C为M2巨噬细胞水平与HCC患者预后的关系; D为MDSC水平与HCC患者预后的关系。

Figure 3. Impact of immune cell infiltration levels on prognosis in HCC patients

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表 1 EXO1 mRNA在不同HCC细胞系中的表达水平比较(x±s)

Table 1. Comparison of EXO1-mRNA expression levels across various HCC cell lines (x±s)

细胞系	n	EXO1相对表达水平
LO2	3	1.00±0.00
BEL-7404	3	3.92±0.75^a
SMMC-7721	3	2.42±0.52^a
Huh7	3	0.66±0.17
Hep3B	3	0.63±0.48
F值		27.620
P值		＜0.001
注：与LO2细胞系比较，^aP＜0.05。

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表 2 基于TCGA数据库分析EXO1表达水平与HCC患者临床病理特征的相关性[例(%)]

Table 2. Correlation analysis between EXO1 expression and clinicopathologic characteristics in HCC based on TCGA database [cases(%)]

项目	EXO1低表达组 (n=187)	EXO1高表达组 (n=187)	统计量	P值
年龄(岁)			2.253^a	0.133
≤60	81(21.7)	96(25.7)
>60	106(28.4)	90(24.1)
性别			2.395^a	0.122
女性	53(14.2)	68(18.2)
男性	134(35.8)	119(31.8)
种族			1.921^a	0.383
亚洲人	72(19.9)	88(24.3)
黑人	8(2.2)	9(2.5)
白人	97(26.8)	88(24.3)
T分期			-3.911^b	＜0.001
T1	112(30.2)	71(19.1)
T2	34(9.2)	61(16.4)
T3	33(8.9)	47(12.7)
T4	5(1.3)	8(2.2)
N分期				0.623^c
N0	124(48.1)	130(50.4)
N1	1(0.4)	3(1.2)
M分期				0.365^c
M0	131(48.2)	137(50.4)
M1	3(1.1)	1(0.4)
组织学分级			-5.461^b	＜0.001
G1	39(10.6)	16(4.3)
G2	101(27.4)	77(20.9)
G3	41(11.1)	83(22.5)
G4	3(0.8)	9(2.4)
病理学分期			-3.825^b	＜0.001
Ⅰ	105(30.0)	68(19.4)
Ⅱ	33(9.4)	54(15.4)
Ⅲ	33(9.4)	52(14.9)
Ⅳ	4(1.1)	1(0.3)
注：^a为χ²值，^b为Z值，^c为采用Fisher精确检验。年龄缺失1例，种族缺失12例，T分期缺失3例，N分期缺失116例，M分期缺失102例，组织学分级缺失5例，病理学分期缺失24例。

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表 3 HCC预后因素的单因素和多因素Cox分析

Table 3. Univariate and multivariate Cox analysis of prognostic factors in HCC

变量	例数	单因素分析		多因素分析
变量	例数	HR(95% CI)	P值	HR (95% CI)	P值
年龄	373	1.205(0.850~1.708)	0.295
性别	373	0.793(0.557~1.130)	0.200
种族	361	1.341(0.926~1.942)	0.121
T分期	370	2.126(1.481~3.052)	＜0.001	0.733(0.101~5.338)	0.759
N分期	258	2.029(0.497~8.281)	0.324
M分期	272	4.077(1.281~12.973)	0.017	4.677(1.383~15.814)	0.013
组织学分级	368	1.091(0.761~1.564)	0.636
病理学分期	349	2.090(1.429~3.055)	＜0.001	2.851(0.381~21.339)	0.308
EXO1表达水平	373	2.036(1.431~2.897)	＜0.001	2.135(1.336~3.413)	0.002
注：年龄缺失1例；性别缺失1例；种族缺失13例；T分期缺失4例；N分期缺失116例；M分期缺失102例；组织学缺失6例；病理学缺失25例；EXO1表达水平缺失1例。各变量赋值方法：年龄，>60岁=1，≤60岁=0；男性=1，女性=0；亚洲人=1，黑人=0，白人=0；T分期，T2~4=1，T1=0；N分期，N1=1，N0=0；M分期，M1=1，M0=0；组织学分级，G3~4=1, G1~2=0；病理学分期，Ⅱ~Ⅳ=1，Ⅰ=0；EXO1，高表达=1，低表达=0。

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