Dataset Information

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

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.

SUBMITTER: Li X

PROVIDER: S-EPMC8922240 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Li Xixi X Liu Zefeng Z Wei Xin X Lin Jie J Yang Qiwei Q Xie Yingjun Y

International journal of general medicine 20220308

<h4>Background</h4>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.<h4>Methods</h4>In this study, we investigated expression levels, clinicopathological correlation, diagnostic and prognostic value, disease associations, co-expression network, functional enrichment, genetic variatio ...[more]

PMID: 35300138

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Project description:ObjectiveThis study aims to build a prognostic model of hepatocellular carcinoma (HCC) with ferroptosis-associated genes and explore their molecular function.MethodsGene expression data and clinical information were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and the International Cancer Genome Consortium (ICGC). A ferroptosis-associated gene set was obtained from the FerrDb database to identify differentially expressed genes. Then, we performed pathway enrichment analysis and immune infiltration analysis. A combined model based on ferroptosis-associated genes for predicting the overall survival of HCC was built by univariate and multivariate Cox regression analyses. Quantitative real-time polymerase chain reaction, Western blotting, colony formation, CCK-8, and EdU incorporation assays were performed to clarify the function of CAPG in the regulation of cell proliferation in human HCC. Ferroptosis was evaluated by glutathione (GSH), malondialdehyde (MDA), and total iron detection.ResultsForty-nine ferroptosis-related genes were significantly correlated with HCC, 19 of which had prognostic significance. CAPG, SLC7A11 and SQSTM1 were used to construct a novel risk model. The areas under the curves (AUCs) were 0.746 and 0.720 (1 year) in the training and validation groups, respectively. The survival analysis indicated that patients with high risk scores exhibited worse survival in the training and validation groups. The risk score was also identified as an independent prognostic factor of overall survival (OS), which established and validated the predictive abilities of the nomogram. The risk score was also significantly correlated with the expression of immune checkpoint genes. In vitro data showed that CAPG knockdown dramatically suppressed HCC cell proliferation, and the underlying molecular mechanisms might be that the silencing of CAPG reduced the expression of SLC7A11 and promoted ferroptosis.ConclusionThe established risk model can be used to predict the prognosis of HCC. At the mechanistic level, CAPG may drive HCC progression by regulating SLC7A11, and ferroptosis activation in HCC patients with high CAPG expression may serve as a potential therapeutic strategy.

Project description:NLRC5, the largest member of the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to participate in the regulation of immune function and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not been fully demonstrated. The aim of this study is to evaluate NLRC5 expression in the tumor tissues of HCC patients undergoing surgical treatment, assess its prognostic value, and explore its relationship with critical immune-related molecules within the tumor microenvironment. A total of 100 patients with hepatitis B virus-associated HCC receiving surgical treatment were enrolled in the study. Immunohistochemical results were obtained by scoring the intensity of cellular staining and the percentage of positive cells in the tissue sections. The association between NLRC5 expression levels and the main clinicopathological factors was analyzed by Chi-square test method. The prognostic values were analyzed by COX regression model and the Kaplan-Meier survival curve. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of NLRC5 in postoperative patients with HCC. IHC showed that high expression of NLRC5 was observed in 67% of HCC tissue samples. Chi-square test showed that NLRC5 was a risk factor associated with tumor number, satellite nodule, and envelope invasion. Kaplan-Meier survival curves and COX survival analysis showed that high expression of NLRC5 was significantly associated with decreased overall survival (OS) in HCC patients (HR = 1.79, 95% CI 1.03-3.12, p = .041). However, univariate logistic regression analysis revealed that NLRC5 showed positive relationship with GZMB and CD8α suggesting its role in immune escape of HCC. ROC curve analysis showed that the combination of tumor number, envelope invasion, and NLRC5 expression (area under the curve = 0.824, sensitivity = 77.30%, specificity = 82.4%) can more accurately evaluate the prognosis of HCC patients compared to the combination of only tumor number and envelope invasion (area under the curve = 0.690, sensitivity = 43.9%, specificity = 94.1%).NLRC5 plays a crucial role in progression of HCC and can be considered as a potential prognostic and predictive biomarker. Targeting NLRC5 may provide an attractive therapeutic approach for HCC.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

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