PDF(Pubmed)
Abstract：
BACKGROUND: Hepatoblastoma (HB) is the most common pediatric liver tumor, presenting significant therapeutic challenges due to its high rates of recurrence and metastasis. While Inosine Monophosphate Dehydrogenase 2(IMPDH2) has been associated with cancer progression, its specific role and clinical implications in HB have not been fully elucidated.
METHODS: This study utilized Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Tissue Microarray (TMA) for validation. Following this, IMPDH2 was suppressed, and a series of in vitro assays were conducted. Flow cytometry was employed to assess apoptosis and cell cycle arrest. Additionally, the study explored the synergistic therapeutic effects of mycophenolate mofetil (MMF) and doxorubicin (DOX) on HB cell lines.
RESULTS: The study identified a marked overexpression of IMPDH2 in HB tissues, which was strongly correlated with reduced Overall Survival (OS) and Event-Free Survival (EFS). IMPDH2 upregulation was also found to be associated with key clinical-pathological features, including pre-chemotherapy alpha-fetoprotein (AFP) levels, presence of preoperative metastasis, and the pre-treatment extent of tumor (PRETEXT) staging system. Knockdown of IMPDH2 significantly inhibited HB cell proliferation and tumorigenicity, inducing cell cycle arrest at the G0/G1 phase. Notably, the combination of MMF, identified as a specific IMPDH2 inhibitor, with DOX, substantially enhanced the therapeutic response.
CONCLUSIONS: The overexpression of IMPDH2 was closely linked to adverse outcomes in HB patients and appeared to accelerate cell cycle progression. These findings suggest that IMPDH2 may serve as a valuable prognostic indicator and a potential therapeutic target for HB.
CONCLUSIONS: The present study unveiled a significant overexpression of inosine monophosphate dehydrogenase 2 (IMPDH2) in hepatoblastoma (HB) tissues, particularly in association with metastasis and recurrence of the disease. The pronounced upregulation of IMPDH2 was found to be intimately correlated with adverse outcomes in HB patients. This overexpression appears to accelerate the progression of the cell cycle, suggesting that IMPDH2 may serve as a promising candidate for both a prognostic marker and a therapeutic target in the context of HB.
METHODS: This study utilized Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Tissue Microarray (TMA) for validation. Following this, IMPDH2 was suppressed, and a series of in vitro assays were conducted. Flow cytometry was employed to assess apoptosis and cell cycle arrest. Additionally, the study explored the synergistic therapeutic effects of mycophenolate mofetil (MMF) and doxorubicin (DOX) on HB cell lines.
RESULTS: The study identified a marked overexpression of IMPDH2 in HB tissues, which was strongly correlated with reduced Overall Survival (OS) and Event-Free Survival (EFS). IMPDH2 upregulation was also found to be associated with key clinical-pathological features, including pre-chemotherapy alpha-fetoprotein (AFP) levels, presence of preoperative metastasis, and the pre-treatment extent of tumor (PRETEXT) staging system. Knockdown of IMPDH2 significantly inhibited HB cell proliferation and tumorigenicity, inducing cell cycle arrest at the G0/G1 phase. Notably, the combination of MMF, identified as a specific IMPDH2 inhibitor, with DOX, substantially enhanced the therapeutic response.
CONCLUSIONS: The overexpression of IMPDH2 was closely linked to adverse outcomes in HB patients and appeared to accelerate cell cycle progression. These findings suggest that IMPDH2 may serve as a valuable prognostic indicator and a potential therapeutic target for HB.
CONCLUSIONS: The present study unveiled a significant overexpression of inosine monophosphate dehydrogenase 2 (IMPDH2) in hepatoblastoma (HB) tissues, particularly in association with metastasis and recurrence of the disease. The pronounced upregulation of IMPDH2 was found to be intimately correlated with adverse outcomes in HB patients. This overexpression appears to accelerate the progression of the cell cycle, suggesting that IMPDH2 may serve as a promising candidate for both a prognostic marker and a therapeutic target in the context of HB.
摘要：
背景：肝母细胞瘤（HB）是最常见的小儿肝脏肿瘤，由于其复发和转移率高，因此提出了重大的治疗挑战。虽然肌苷一磷酸脱氢酶2（IMPDH2）与癌症进展有关，其在乙型肝炎中的具体作用和临床意义尚未完全阐明。
方法:本研究利用定量实时聚合酶链反应(qRT-PCR)和组织微阵列(TMA)进行验证。在此之后,IMPDH2被抑制，并进行了一系列体外试验。流式细胞术用于评估细胞凋亡和细胞周期停滞。此外,本研究探讨了霉酚酸酯（MMF）和多柔比星（DOX）对HB细胞系的协同治疗作用。
结果：该研究发现在HB组织中IMPDH2显著过表达，与总生存率（OS）和无事件生存率（EFS）降低密切相关。还发现IMPDH2上调与关键的临床病理特征有关。包括化疗前甲胎蛋白（AFP）水平，术前转移的存在，和肿瘤治疗前程度（PRETEXT）分期系统。敲除IMPDH2显著抑制HB细胞增殖和致瘤性,诱导细胞周期阻滞在G0/G1期。值得注意的是,MMF的组合，鉴定为特异性IMPDH2抑制剂，DOX,大大增强了治疗反应。
结论：IMPDH2的过表达与HB患者的不良结局密切相关，并且似乎加速了细胞周期的进展。这些发现表明IMPDH2可作为HB的有价值的预后指标和潜在的治疗靶标。
结论：本研究揭示了肝母细胞瘤（HB）组织中肌苷一磷酸脱氢酶2（IMPDH2）的显著过表达，特别是与疾病的转移和复发有关。发现IMPDH2的明显上调与HB患者的不良结局密切相关。这种过度表达似乎加速了细胞周期的进程，这表明IMPDH2可能是HB背景下的预后标志物和治疗靶标的有希望的候选者。
方法:本研究利用定量实时聚合酶链反应(qRT-PCR)和组织微阵列(TMA)进行验证。在此之后,IMPDH2被抑制，并进行了一系列体外试验。流式细胞术用于评估细胞凋亡和细胞周期停滞。此外,本研究探讨了霉酚酸酯（MMF）和多柔比星（DOX）对HB细胞系的协同治疗作用。
结果：该研究发现在HB组织中IMPDH2显著过表达，与总生存率（OS）和无事件生存率（EFS）降低密切相关。还发现IMPDH2上调与关键的临床病理特征有关。包括化疗前甲胎蛋白（AFP）水平，术前转移的存在，和肿瘤治疗前程度（PRETEXT）分期系统。敲除IMPDH2显著抑制HB细胞增殖和致瘤性,诱导细胞周期阻滞在G0/G1期。值得注意的是,MMF的组合，鉴定为特异性IMPDH2抑制剂，DOX,大大增强了治疗反应。
结论：IMPDH2的过表达与HB患者的不良结局密切相关，并且似乎加速了细胞周期的进展。这些发现表明IMPDH2可作为HB的有价值的预后指标和潜在的治疗靶标。
结论：本研究揭示了肝母细胞瘤（HB）组织中肌苷一磷酸脱氢酶2（IMPDH2）的显著过表达，特别是与疾病的转移和复发有关。发现IMPDH2的明显上调与HB患者的不良结局密切相关。这种过度表达似乎加速了细胞周期的进程，这表明IMPDH2可能是HB背景下的预后标志物和治疗靶标的有希望的候选者。
