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肝细胞癌中THO复合体成员的表达及临床意义的综合分析

Comprehensive Analysis of the Expression and Clinical Significance of THO Complex Members in Hepatocellular Carcinoma.

作者信息

Li Xixi, Liu Zefeng, Wei Xin, Lin Jie, Yang Qiwei, Xie Yingjun

机构信息

Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, People's Republic of China.

Medical Research Center, The Second Hospital of Jilin University, Changchun, People's Republic of China.

出版信息

Int J Gen Med. 2022 Mar 8;15:2695-2713. doi: 10.2147/IJGM.S349925. eCollection 2022.

Abstract

BACKGROUND

THO complex members (THOCs) are essential for mRNA processing, transcription elongation, mRNA export and genome integrity, which may be associated with tumor. However, the significance of THO complex members in Hepatocellular carcinoma (HCC) has not been clarified.

METHODS

In this study, we investigated expression levels, clinicopathological correlation, diagnostic and prognostic value, disease associations, co-expression network, functional enrichment, genetic variation, drug sensitivity, molecular targets, and immune infiltration of THOCs in HCC using UALCAN, ICGC, HPA, Kaplan-Meier Plotter, The Open Targets Platform database, GeneMANIA, WebGestalt, GSCALite, LinkedOmics, TIMER. Meanwhile, the mRNA expression levels of THOCs in HCC were verified by qRT-PCR.

RESULTS

THOCs were significantly up-regulated at the transcription level in HCC, and overexpression of THOCs was correlated with clinicopathological features. THOCs had potential diagnostic and prognostic value for HCC. THOCs could participate in apoptosis, regulate cell cycle, and were also involved in DNA damage response. Important cancer-related signaling pathways such as EMT, RAS/MAPK pathway and RKT pathway were also related to THOCs expression. In addition, the expression level of THOC1/2/6/7 was negatively correlated with drug resistance. And miRNA, kinase, and transcription factor targets associated with THOCs have been identified. Meanwhile, THOCs were associated with immune infiltration in HCC.

CONCLUSION

Our study revealed that THO complex members have important clinical significance for HCC and have potential clinical utility in diagnosis, treatment and prognosis.

摘要

背景

THO复合体成员(THOCs)对于mRNA加工、转录延伸、mRNA输出和基因组完整性至关重要,这些可能与肿瘤相关。然而,THO复合体成员在肝细胞癌(HCC)中的意义尚未阐明。

方法

在本研究中,我们使用UALCAN、ICGC、HPA、Kaplan-Meier Plotter、The Open Targets Platform数据库、GeneMANIA、WebGestalt、GSCALite、LinkedOmics、TIMER研究了HCC中THOCs的表达水平、临床病理相关性、诊断和预后价值、疾病关联、共表达网络、功能富集、基因变异、药物敏感性、分子靶点和免疫浸润。同时,通过qRT-PCR验证了HCC中THOCs的mRNA表达水平。

结果

THOCs在HCC的转录水平上显著上调,且THOCs的过表达与临床病理特征相关。THOCs对HCC具有潜在的诊断和预后价值。THOCs可参与细胞凋亡、调节细胞周期,还参与DNA损伤反应。重要的癌症相关信号通路如EMT、RAS/MAPK通路和RKT通路也与THOCs表达相关。此外,THOC1/2/6/7的表达水平与耐药性呈负相关。并且已鉴定出与THOCs相关的miRNA、激酶和转录因子靶点。同时,THOCs与HCC中的免疫浸润相关。

结论

我们的研究表明,THO复合体成员对HCC具有重要的临床意义,在诊断、治疗和预后方面具有潜在的临床应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a86/8922240/3d65495bf37f/IJGM-15-2695-g0001.jpg

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