基于UCSC数据库的肝细胞癌ceRNA网络构建与预后的关系

邱天; 屈翔宇; 李浩令; 夏文庆; 戴恒文; 顾林

doi:10.16766/j.cnki.issn.1674-4152.003816

基于UCSC数据库的肝细胞癌ceRNA网络构建与预后的关系

doi: 10.16766/j.cnki.issn.1674-4152.003816

1.
蚌埠医科大学临床医学院，安徽蚌埠 233000
2.
蚌埠医科大学第一附属医院消化内科，安徽蚌埠 233004

基金项目:

安徽省高校自然科学研究重点项目 2022AH051489

安徽省大学生创新创业训练计划 S202210367142

详细信息

通讯作者:
顾林，E-mail：27692848@qq.com

中图分类号: R735.7 R730.7
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- 文章访问数: 16
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- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2024-02-13
- 网络出版日期: 2025-01-20

The relationship between ceRNA network construction and prognosis of hepatocellular carcinoma based on UCSC database

1.
School of Clinical Medicine, Bengbu Medical University, Bengbu, Anhui 233000, China

摘要

摘要: 目的构建并探讨肝细胞肝癌中与预后相关的竞争性内源性RNA网络及其临床应用前景。方法从UCSC Xena数据库中获得肝细胞肝癌的基因RNA、mRNA测序数据和临床相关数据。首先使用差异分析和生存分析筛选目标高风险基因，并通过KS检验、逻辑回归、单因素及多因素Cox分析研究该基因是否可以作为独立预后因子，进一步行GO分析和KEGG分析研究其潜在的生物通路。此后, 使用ENCORI进行miRNA靶基因预测并利用在线预测工具cyoscape构建了相应的ceRNA网络。结果 hsa-miR-101-3p与25个lncRNA之间具有直接调控关系，有6个lncRNA可以与miRNA竞争性结合。其中GSEC与hsa-miR-101-3p、STIP1共表达相关性最为显著(r=-0.380, r=0.490)，可能作为一种调节轴在调控HCC增殖、侵袭、凋亡等方面起重要作用。结论本研究展示的肝细胞癌中STIP1/hsa-miR-101-3p/lncRNA GSEC调控网络有助于更好地了解肝细胞肝癌发生发展过程中的分子生物学机制，展示的lncRNA可能成为肝癌患者潜在的预后生物标志物。
- 肝细胞癌 /
- 竞争性内源性RNA /
- 长链非编码RNA /
- 预后标志物
Abstract: Objective To construct and investigate a prognostic-related competitive endogenous RNA network in hepatocellular carcinoma and explore its clinical implications. Methods The genetic RNA, mRNA sequencing data, and clinical data for HCC were obtained from the UCSC Xena database. Firstly, differential expression and survival analyses were used to identify high-risk genes. The KS test, logistic regression, and univariate and multivariate Cox regression analyses were used to determine the potential of these genes as independent prognostic factors. The associated biological pathways were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. After that, ENCORI was used to predict miRNA target genes. The ceRNA network was constructed using the Cytoscape tool. Results A direct regulatory relationship was found between hsa-miR-101-3p and 25 lncRNAs, with 6 lncRNAs identified as competitive binders to miRNAs. Among them, GSEC exhibited the strongest correlation with the co-expression of hsa-miR-101-3p and STIP1 (r=-0.380, r=0.490), suggesting its potential role as a regulatory axis in regulating hepatocellular carcinoma proliferation, invasion, and apoptosis. Conclusion The regulatory network of STIP1/hsa-miR-101-3p/lncRNA GSEC identified in hepatocellular carcinoma provides valuable insights into the molecular biological mechanisms of HCC, and lncRNA may serve as a potential prognostic biomarker for HCC patients.
- Hepatocellular carcinoma /
- Competitive endogenous RNA /
- Long non-coding RNA /
- Prognostic markers

HTML全文

图 1 TIMER网站分析TCGA数据库中不同癌症类型中STIP1的表达情况

Figure 1. TIMER website analysis of STIP1 expression in different cancer types in the TCGA database

下载: 全尺寸图片幻灯片

图 2 STIP1在肿瘤组与对照组之间的生存分析曲线

Figure 2. Survival analysis curves of STIP1 between the tumor and control groups

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图 3 hsa-miR-101-3p的生存分析与共表达分析

Figure 3. Survival and co-expression analysis of hsa-miR-101-3p

下载: 全尺寸图片幻灯片

图 4 GSEC共表达分析

Figure 4. Co-expression analysis of GSECs

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图 5 调控网络构建

注：A为miRNA-mRNA-lncRNA调控网络可视化；B为STIP1调控的ceRNA网络。

Figure 5. Regulation network construction

下载: 全尺寸图片幻灯片

表 1 STIP1单因素Cox分析

Table 1. Univariate Cox analysis of STIP1

变量	HR(95% CI)	P值
年龄	1.007(0.989~1.025)	0.480
性别	0.778(0.487~1.244)	0.295
分级	1.013(0.743~1.380)	0.934
分期	1.879(1.466~2.408)	＜0.001
T	1.816(1.443~2.287)	＜0.001
M	3.924(1.230~12.519)	0.021
N	2.070(0.506~8.471)	0.312
STIP1	2.375(1.667~3.385)	＜0.001

下载: 导出CSV

表 2 STIP1多因素Cox分析

Table 2. Multivariate Cox analysis of STIP1

变量	HR(95% CI)	P值
年龄	1.014(0.994~1.034)	0.168
性别	1.028(0.609~1.736)	0.917
分级	0.950(0.673~1.341)	0.770
分期	0.951(0.359~2.521)	0.919
T	1.741(0.728~4.168)	0.213
M	1.502(0.397~5.686)	0.549
N	1.927(0.304~12.223)	0.487
STIP1	2.234(1.520~3.286)	＜0.001

下载: 导出CSV

参考文献(20)

[1]	甘景卓. 原发性肝癌中LncRNA OSER1-AS1与miR-612表达的相关性及生物学意义[J]. 现代消化及介入诊疗, 2022, 27(1): 45-50. GAN J Z. Correlation and biological significance of LncRNA OSER1-AS1 and miR-612 expression in primary hepatocellular carcinoma[J]. Modern Gastroenterology and Interventional Diagnosis and Treatment, 2022, 27(1): 45-50.
[2]	黎作茶, 韦武均, 韦彩成, 等. lncRNA RP5-940J5.9表达水平与肝细胞癌患者预后相关性研究[J]. 右江医学, 2022, 50(3): 181-185. LI Z T, WEI W J, WEI C C, et al. Correlation between lncRNA RP5-940J5.9 expression level and prognosis of patients with hepatocellular carcinoma[J]. Youjiang Medicine, 2022, 50(3): 181-185.
[3]	盖智敏, 陈颖丽, 刘姝含, 等. 细胞质lncRNA在ceRNA网络中对肝癌的预后作用[J]. 内蒙古大学学报(自然科学版), 2024, 55(1): 54-64. GAI Z M, CHEN Y L, LIU S H, et al. Prognostic effect of cytoplasmic lncRNA in ceRNA network on liver cancer[J]. Journal of Inner Mongolia University(Natural Science Edition), 2024, 55(1): 54-64.
[4]	孙永红, 陈永林. 胃癌相关长链非编码RNA的作用及其意义[J]. 临床与病理杂志, 2021, 41(4): 892-898. SUN Y H, CHEN Y L. The role and significance of long non-coding RNA related to gastric cancer[J]. Journal of Clinical and Pathology, 2021, 41(4): 892-898.
[5]	HUANG S, ZHANG J, LAI X, et al. Identification of novel tumor microenvironment-related long noncoding RNAs to determine the prognosis and response to immunotherapy of hepatocellular carcinoma patients[J]. Front Mol Biosci, 2021, 8: 781307. DOI: 10.3389/fmolb.2021.781307.
[6]	周倩, 邵建国. MiRNA在HBV相关肝癌中的研究进展[J]. 南通大学学报(医学版), 2022, 42(3): 257-261. ZHOU Q, SHAO J G. Research progress of MiRNA in HBV-associated liver cancer[J]. Journal of Nantong University(Medical Science), 2022, 42(3): 257-261.
[7]	ZHANG Y, LUO M, CUI X, et al. Long noncoding RNA NEAT1 promotes ferroptosis by modulating the miR-362-3p/MIOX axis as a ceRNA[J]. Cell Death Differ, 2022, 29(9): 1850-1863. doi: 10.1038/s41418-022-00970-9
[8]	夏文广, 张浩, 魏川雄, 等. 甲状腺乳头状癌相关ceRNA网络的生物信息学分析[J]. 中华全科医学, 2023, 21(4): 693-697. doi: 10.16766/j.cnki.issn.1674-4152.002962 XIA W G, ZHANG H, WEI C X, et al. Bioinformatics analysis of ceRNA network related to papillary thyroid carcinoma[J]. Chinese Journal of General Practice, 2023, 21(4): 693-697. doi: 10.16766/j.cnki.issn.1674-4152.002962
[9]	卢春苗, 莫书天, 韩创业, 等. KIF2C在肝细胞癌中的作用及ceRNA调控网络构建[J]. 广西医科大学学报, 2023, 40(2): 189-198. LU C M, MO S T, HAN C Y, et al. The role of KIF2C in hepatocellular carcinoma and the construction of ceRNA regulatory network[J]. Journal of Guangxi Medical University, 2023, 40(2): 189-198.
[10]	闵航. LncRNA GSEC通过miR-101-3p/PSPH/VEGF轴调控肝细胞癌进展的机制研究[D]. 武汉: 武汉科技大学, 2023. MIN H. Mechanism of LncRNA GSEC regulating hepatocellular carcinoma progression through miR-101-3p/PSPH/VEGF axis[D]. Wuhan: Wuhan University of Science and Technology, 2023.
[11]	张静, 张晓, 张瑞, 等. miR-101-3p通过靶向抑制斯坦尼钙调节蛋白1(STC1)促进巨噬细胞对人肝癌细胞的吞噬作用[J]. 细胞与分子免疫学杂志, 2023, 39(4): 339-344. ZHANG J, ZHANG X, ZHANG R, et al. miR-101-3p promotes macrophage phagocytosis of human hepatocellular carcinoma cells by targeting inhibition of Stanley calmodulin 1 (STC1)[J]. Journal of Cell and Molecular Immunology, 2023, 39(4): 339-344.
[12]	邵毅博, 王春莉, 杨力. miR-101在肝癌发展中的作用研究[J]. 医用生物力学, 2021, 36(S1): 332. SHAO Y B, WANG C L, YANG L. Study of the role of miR-101 in the development of liver cancer[J]. Medical Biomechanics, 2021, 36(S1): 332.
[13]	MA X L, TANG W G, YANG M J, et al. Serum STIP1, a novel indicator for microvascular invasion, predicts outcomes and treatment response in hepatocellular carcinoma[J]. Front Oncol, 2020, 10: 511. DOI: 10.3389/fonc.2020.00511.
[14]	CHAO A, LIAO M J, CHEN S H, et al. JAK2-Mediated phosphorylation of stress-induced phosphoprotein-1 (STIP1) in human cells[J]. Int J Mol Sci, 2022, 23(5): 2420. DOI: 10.3390/ijms23052420.
[15]	DOURADO M R, ELSERAGY A, DA COSTA B C, et al. Stress induced phosphoprotein 1 overexpression controls proliferation, migration and invasion and is associated with poor survival in oral squamous cell carcinoma[J]. Front Oncol, 2023, 12: 1085917. DOI: 10.3389/fonc.2022.1085917.
[16]	XIA Y, CHEN J, LIU G, et al. STIP1 knockdown suppresses colorectal cancer cell proliferation, migration and invasion by inhibiting STAT3 pathway[J]. Chem Biol Interact, 2021, 341: 109446. DOI: 10.1016/j.cbi.2021.109446.
[17]	KRAFFT U, TSCHIRDEWAHN S, HESS J, et al. STIP1 tissue expression is associated with survival in chemotherapy-treated bladder cancer patients[J]. Pathol Oncol Res, 2020, 26(2): 1243-1249. doi: 10.1007/s12253-019-00689-y
[18]	LI R, LI P, WANG J, et al. STIP1 down-regulation inhibits glycolysis by suppressing PKM2 and LDHA and inactivating the Wnt/β-catenin pathway in cervical carcinoma cells[J]. Life Sci, 2020, 258: 118190. DOI: 10.1016/j.lfs.2020.118190.
[19]	WANG J H, GONG C, GUO F J, et al. Knockdown of STIP1 inhibits the invasion of CD133 positive cancer stem like cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways[J]. Int J Mol Med, 2020, 46(6): 2251-2259.
[20]	WANG K, JIANG S, HUANG A, et al. GOLPH3 promotes cancer growth by interacting with STIP1 and regulating telomerase activity in pancreatic ductal adenocarcinoma[J]. Front Oncol, 2020, 10: 575358. DOI: 10.3389/fonc.2020.575358.