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

Frontiers in Oncology

Meigui Xiao¹  Letao Lin¹  Xi Chen¹  Fujun Zhang¹  Zhenyu Li¹  Guanyu Chen¹  Huzheng Yan²  Xu He⁴  Yanling Zhang⁵ 

[1] Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China;Department of Interventional Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China;Interventional Medical Center, Zhuhai People’s Hospital, Zhuhai, China;School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China;State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China;

关键词: liver hepatocellular carcinoma;    DEAH-box RNA helicases;    DHX9;    radiosensitivity;    DNA repair;   

DOI  :  10.3389/fonc.2022.900671

来源: DOAJ

【 摘 要 】

BackgroundLiver hepatocellular carcinoma (LIHC), one of the most common primary malignancies, exhibits high levels of molecular and clinical heterogeneity. Increasing evidence has confirmed the important roles of some RNA helicase families in tumor development, but the function of the DEAH-box RNA helicase family in LIHC therapeutic strategies has not yet been clarified.MethodsThe LIHC dataset was downloaded from The Cancer Genome Atlas (TCGA). Consensus clustering was applied to group the patients. Least absolute shrinkage and selection operator Cox regression and univariate and multivariate Cox regression were used to develop and validate a prognostic risk model. The Tumor Immune Estimation Resource and Tumor Immune Single Cell Hub databases were used to explore the role of DEAH-box RNA helicases in LIHC immunotherapy. In vitro experiments were performed to investigate the role of DHX9 in LIHC radiosensitivity.ResultsTwelve survival-related DEAH-box RNA helicases were identified. High helicase expression levels were associated with a poor prognosis and clinical features. A prognostic model comprising six DEAH-box RNA helicases (DHX8, DHX9, DHX34, DHX35, DHX38, and DHX57) was constructed. The risk score of this model was found to be an independent prognostic indicator, and LIHC patients with different prognosis were distinguished by the model in the training and test cohorts. DNA damage repair pathways were also enriched in patients with high-risk scores. The six DEAH-box RNA helicases in the risk model were substantially related to innate immune cell infiltration and immune inhibitors. In vitro experiments showed that DHX9 knockdown improved radiosensitivity by increasing DNA damage.ConclusionThe DEAH-box RNA helicase signature can be used as a reliable prognostic biomarker for LIHC. In addition, DHX9 may be a definitive indicator and therapeutic target in radiotherapy and immunotherapy for LIHC.

【 授权许可】

Unknown