Liver 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.The 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.Twelve 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.The 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.
Abstract The relative abundance of myeloid‐derived suppressor cells (MDSCs) compared to cytotoxic T cells determines the outcomes of diseases and the efficacy of immunotherapy. Ubiquitin‐specific peptidase 12 (USP12), a member of the USP family of deubiquitinases, targets multiple signalling pathways and regulates diverse biological processes, including cell proliferation and survival. It is well known that ubiquitylation is an important mechanism for regulating the immune response. However, it is unclear whether USP12 regulates tumour growth by influencing MDSCs. In the present study, we reported that USP12 deficiency decreased infiltration and impaired the suppressor function of monocytic (M)‐MDSCs, resulting in increased CD8 + T‐cell response and decelerated tumour growth. USP12‐knockout M‐MDSCs were less potent in inhibiting the proliferation of CD8 + T cells and their ability to secrete IFN‐γ. Furthermore, USP12 deficiency inhibited the suppressor function of M‐MDSCs by downregulating the negative regulatory molecules inducible nitric oxide synthase and PD‐L1, through deubiquitinating and stabilizing p65. Our results suggest that USP12 is a positive regulator of M‐MDSCs and may serve as a potential target for antitumor therapy.
The aim of this study was to compare the effectiveness and outcomes of percutaneous ablation guided by ultrasonography (US) and computed tomography (CT) in colorectal liver oligometastases (CLOM).This study included patients with CLOM treated with percutaneous ablation from January 2008 to January 2021 in this observational study. Only lesions visualized on both CT and US images were further analyzed according to whether patients' initial ablation treatments utilized US guidance or CT guidance. The Kaplan-Meier method was used to estimate local tumor progression (LTP)-free survival after propensity score matching (PSM). The LTP-free survival and treatment-related outcomes were compared between these two groups.PSM identified 116 patients from each group, with 269 and 238 lesions in the USguided and CT-guided groups, respectively. US-guided ablation had a shorter average procedure time and lower cost than CT-guided ablation (27.54±12.06 minutes vs. 32.70±13.88 minutes, P=0.003; $2,175.13±618.17 vs. $2,455.49±710.25, P=0.002). For patients >60 years of age, the cumulative LTP rate at 1 year was lower in the US-guided group than in the CT-guided group (17.8% vs. 25.1%, P=0.038). For patients with perivascular liver lesions, the cumulative LTP rate at 1 year was lower in the US-guided group (14.4% vs. 28.2%, P=0.040).For patients whose age is >60 years or who have perivascular liver lesions, USguided ablation is better than CT-guided ablation, with a shorter treatment time and lower costs when both ablation methods are feasible for patients.
Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including 125I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)-derived from exons 2-6 of EYA3-facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC 125I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under 125I and X-ray irradiation conditions.CircEYA3 was identified by RNA-seq in patients with HCC before and after 125I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with 125I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model.CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells.Our findings demonstrate that circEYA3 increases the radioresistance of HCC to 125I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.
The discrepancy between the high technical success rate and the relatively low clinical response rate of renal artery stenting (RAS) raises the importance to identify atherosclerotic renal artery stenosis (ARAS) patients who are most likely to benefit from RAS. This study aimed to investigate the feasibility and accuracy of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) in predicting split renal function (SRF) improvement after RAS in patients with ARAS.Thirty patients with severe ARAS who were treated with RAS were enrolled. Baseline cortical and medullary R2* values of each kidney were measured by BOLD-MRI, and each patient's SRF was evaluated by nuclear renal dynamic imaging at baseline and 1-month follow-up.In total, 35 severe stenotic renal arteries of the 30 patients were analyzed. At 1-month follow-up, 34 kidneys (97.1%) of severe ARAS had acquired SRF. SRF improved in 12 kidneys of 10 patients. The cortical R2* and medullary R2* values in the SRF improvement kidneys were higher than those in the non-improvement kidneys (P ≤ 0.001). The area under the curve of medullary R2* was 0.879 (95% confidence interval [CI] 0.736-1.000). A medullary R2* value ≥29.1 s-1 was noted to provide good sensitivity (0.833, 95% CI 0.552-0.970) and specificity (0.864, 95% CI 0.667-0.953) in predicting SRF improvement. Medullary R2* value was the only independent predictor of SRF improvement in multivariable analysis (P = 0.034, OR 3.017, 95%CI 1.089-8.358).This study showed that a BOLD-MRI medullary R2* value ≥29.1 s-1 was an excellent predictor of SRF improvement in patients with severe ARAS who underwent renal artery stenting.
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