AUTHOR=Chen Xi , Lin Letao , Chen Guanyu , Yan Huzheng , Li Zhenyu , Xiao Meigui , He Xu , Zhang Fujun , Zhang Yanling 

TITLE=High Levels of DEAH-Box Helicases Relate to Poor Prognosis and Reduction of DHX9 Improves Radiosensitivity of Hepatocellular Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.900671

DOI=10.3389/fonc.2022.900671

ISSN=2234-943X

ABSTRACT=Background: Liver hepatocellular carcinoma (LIHC), one of the most 
common primary malignancies, exhibits high levels of molecular and 
clinical heterogeneity. Accumulating evidence has confirmed the 
important roles of some RNA helicase family in tumor development, but 
the function of DEAH-box RNA helicase families in LIHC therapeutic 
strategies has not yet been clarified. 
Methods: The Cancer Genome Atlas (TCGA) was used to download the 
LIHC dataset. Consensus clustering were applied to group the patients.
Least absolute shrinkage and selection operator Cox (Lasso) regression 
and univariate and multivariate Cox regression were used to develop 
and validate a prognostic risk model. Timer online databases and Tumor 
Immune Single Cell Hub (TISCH) were applied to explore the role of 
DEAH-box RNA helicases in LIHC immunotherapy. In vitro experiments 
were performed to explore the role of DHX9 in LIHC radiosensitivity.
Results: Twelve survival-related DEAH-box RNA helicases were 
identified. High helicase expression levels are associated with a poor 
prognosis and worse clinical features. A prognostic model composed of 
six DEAH-box RNA helicases (DHX8, DHX9, DHX34, DHX35, DHX38, and 
DHX57) was constructed. It was confirmed that the risk score of this 
model could be an independent prognostic indicator, and that LIHC 
patients with different prognoses could be distinguished by the model 
in the training and test cohorts from TCGA. DNA repair pathways were 
also enriched in patients with high-risk scores. 6 DEAH-box RNA
helicases from the risk model were significantly related to innate 
immune cells infiltration and immune inhibitors. In vitro experiments we 
confirmed that DHX9 knockdown improves radiosensitivity by 
increasing DNA damage.
Conclusion: The DEAH-box RNA helicase signature can be used as a 
reliable biomarker for the prognosis of LIHC. In addition, DHX9 may act 
as trustworthy indicators and therapeutic targets in radiotherapy and 
immunotherapy for LIHC.