DHX37 Impacts Prognosis of Hepatocellular Carcinoma and Lung Adenocarcinoma through Immune Infiltration

Xu, Yanan; Jiang, Qiongchao; Liu, Hejun; Xiao, Xiaoyun; Yang, Dinghong; Saw, Phei Er; Luo, Baoming

doi:10.1155/2020/8835393

Cited by 10 publications

(5 citation statements)

References 57 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DHX37 is an RNA helicase, which is significantly upregulated in 17 kinds of tumors ( Huang et al, 2021 ). DHX37 could affect the prognosis of patients with HCC or lung adenocarcinoma by immune infiltration, and can be used as a prognostic biomarker for HCC and lung adenocarcinoma ( Xu et al, 2020 ; Chen et al, 2022 ). Moreover, DHX37 acts as a function regulator of CD8 T cells ( Dong et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Machine Learning Screens Potential Drugs Targeting a Prognostic Gene Signature Associated With Proliferation in Hepatocellular Carcinoma

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Background: This study aimed to screen potential drugs targeting a new prognostic gene signature associated with proliferation in hepatocellular carcinoma (HCC).Methods: CRISPR Library and TCGA datasets were used to explore differentially expressed genes (DEGs) related to the proliferation of HCC cells. Differential gene expression analysis, univariate COX regression analysis, random forest algorithm and multiple combinatorial screening were used to construct a prognostic gene signature. Then the predictive power of the gene signature was validated in the TCGA and ICGC datasets. Furthermore, potential drugs targeting this gene signature were screened.Results: A total of 640 DEGs related to HCC proliferation were identified. Using univariate Cox analysis and random forest algorithm, 10 hub genes were screened. Subsequently, using multiplex combinatorial screening, five hub genes (FARSB, NOP58, CCT4, DHX37 and YARS) were identified. Taking the median risk score as a cutoff value, HCC patients were divided into high- and low-risk groups. Kaplan-Meier analysis performed in the training set showed that the overall survival of the high-risk group was worse than that of the low-risk group (p < 0.001). The ROC curve showed a good predictive efficiency of the risk score (AUC > 0.699). The risk score was related to gene mutation, cancer cell stemness and immune function changes. Prediction of immunotherapy suggetsted the IC50s of immune checkpoint inhibitors including A-443654, ABT-888, AG-014699, ATRA, AUY-922, and AZ-628 in the high-risk group were lower than those in the low-risk group, while the IC50s of AMG-706, A-770041, AICAR, AKT inhibitor VIII, Axitinib, and AZD-0530 in the high-risk group were higher than those in the low-risk group. Drug sensitivity analysis indicated that FARSB was positively correlated with Hydroxyurea, Vorinostat, Nelarabine, and Lomustine, while negatively correlated with JNJ-42756493. DHX37 was positively correlated with Raltitrexed, Cytarabine, Cisplatin, Tiotepa, and Triethylene Melamine. YARS was positively correlated with Axitinib, Fluphenazine and Megestrol acetate. NOP58 was positively correlated with Vorinostat and 6-thioguanine. CCT4 was positively correlated with Nerabine.Conclusion: The five-gene signature associated with proliferation can be used for survival prediction and risk stratification for HCC patients. Potential drugs targeting this gene signature deserve further attention in the treatment of HCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Machine Learning Screens Potential Drugs Targeting a Prognostic Gene Signature Associated With Proliferation in Hepatocellular Carcinoma

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…For example, Wang et al [ 23 ] established a LUAD prognostic nomogram comprising immune-infiltrating Treg-related genes. In addition, DHX37 influences the prognosis of LUAD through immune cell infiltration [ 24 ]. Moreover, Fan et al [ 25 ] demonstrated that multiple immune cell subtypes infiltration was closely related to LUAD prognosis.…”

Section: Discussionmentioning

confidence: 99%

Construction of an immune-related lncRNA signature as a novel prognosis biomarker for LUAD

Chen

Shen²,

et al. 2021

Aging

View full text Add to dashboard Cite

The tumor immune microenvironment of lung cancer is associated with prognosis and immunotherapy efficacy. Long noncoding RNAs are identified as prognostic biomarkers associated with immune functions. We constructed a signature comprising differentially expressed immune-related lncRNAs to predict the prognosis of patients with lung adenocarcinoma. We established the immune-related lncRNA signature by pairing immune-related lncRNAs regardless of expression level and lung adenocarcinoma patients were divided into high- and low-risk groups. The prognosis of patients in the two groups was significantly different; The immune-related lncRNA signature could serve as an independent lung adenocarcinoma prognostic indicator. The signature correlated negatively with B cell, CD4+ T cell, M2 macrophage, neutrophil, and monocyte immune infiltration. Patients with low risk scores had a higher abundance of immune cells and stromal cells around the tumor. Gene set enrichment analysis showed that samples from low-risk group were more active in the IgA production in intestinal immune network and the T and B cell receptor signaling pathway. High-risk groups had significant involvement of the cell cycle, DNA replication, adherens junction, actin cytoskeleton regulation, pathways in cancer, and TGF-β signaling pathways. High risk scores correlated significantly negatively with high CTLA-4 and HAVCR2 expression and higher median inhibitory concentration of common anti-tumor chemotherapeutics (e.g., cisplatin, paclitaxel, gemcitabine) and targeted therapy (e.g., erlotinib and gefitinib). We identified a reliable immune-related lncRNA lung adenocarcinoma prognosis model, and the immune-related lncRNA signature showed promising clinical prediction value.

show abstract

“…Recent bioinformatic analysis of DHX37 expression profiles in multiple have cancers also shown that DHX37 is a potential marker and is associated with the tumor immune microenvironment in liver cancer (9)(10)(11). However, the molecular mechanisms underlying the pro-oncogenic role of DHX37 in liver cancer remain largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

RNA Helicase DHX37 Facilitates Liver Cancer Progression by Cooperating with PLRG1 to Drive Superenhancer-Mediated Transcription of Cyclin D1

Liu

et al. 2022

Cancer Research

View full text Add to dashboard Cite

RNA helicases are dysregulated in tumors. Here, we identified DHX37 as one of the top RNA helicase genes with upregulated expression in hepatocellular carcinoma (HCC). DHX37 promoted proliferation of liver cancer cells in vitro and in vivo. Epigenomic profiling of DHX37-knockdown and control HCC cells revealed that DHX37 is associated with super enhancer activity. Mechanistically, DHX37 interacted with pleiotropic regulator 1 (PLRG1) to transcriptionally activate cyclin D1 (CCND1) expression via co-occupation of its promoter and super enhancer elements. DHX37 and PLRG1 promoted liver cancer cell proliferation and contributed to the poor prognosis of HCC patients. Importantly, CCND1 inhibitors were effective as antiproliferative agents for liver cancer. These results together demonstrate a cooperative mechanistic interaction between DHX37 and PLRG1 that regulates CCND1 expression and promotes liver cancer progression, advancing our understanding of the epigenetic and transcriptional dysregulations mediated by RNA helicases and super enhancers in HCC.

show abstract

DHX37 Impacts Prognosis of Hepatocellular Carcinoma and Lung Adenocarcinoma through Immune Infiltration

Cited by 10 publications

References 57 publications

Machine Learning Screens Potential Drugs Targeting a Prognostic Gene Signature Associated With Proliferation in Hepatocellular Carcinoma

Machine Learning Screens Potential Drugs Targeting a Prognostic Gene Signature Associated With Proliferation in Hepatocellular Carcinoma

Construction of an immune-related lncRNA signature as a novel prognosis biomarker for LUAD

RNA Helicase DHX37 Facilitates Liver Cancer Progression by Cooperating with PLRG1 to Drive Superenhancer-Mediated Transcription of Cyclin D1

Contact Info

Product

Resources

About