Li Linman, Wu Yichi, Huang Hong-Ting, Yong June-Kong, Lv Zicheng, Zhou Yi, Xiang Xuelin, Zhao Jie, Xi Zhifeng, Feng Hao, Xia Qiang
Department of Liver Surgery, Renji Hospital (Punan Branch), School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Shanghai Engineering Research Centre of Transplantation and Immunology, Shanghai, 200127, China.
J Cancer Res Clin Oncol. 2024 Aug 1;150(8):377. doi: 10.1007/s00432-024-05858-4.
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.
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.
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.
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.
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.
肝母细胞瘤（HB）是最常见的儿童肝脏肿瘤，因其高复发率和转移率而带来重大治疗挑战。虽然肌苷单磷酸脱氢酶2（IMPDH2）与癌症进展有关，但其在HB中的具体作用和临床意义尚未完全阐明。
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，抑制IMPDH2，并进行一系列体外试验。采用流式细胞术评估细胞凋亡和细胞周期阻滞。此外，该研究探讨了霉酚酸酯（MMF）和阿霉素（DOX）对HB细胞系的协同治疗效果。
该研究发现HB组织中IMPDH2明显过表达，这与总生存期（OS）和无事件生存期（EFS）降低密切相关。还发现IMPDH2上调与关键临床病理特征有关，包括化疗前甲胎蛋白（AFP）水平、术前转移的存在以及肿瘤预处理范围（PRETEXT）分期系统。抑制IMPDH2可显著抑制HB细胞增殖和致瘤性，并诱导细胞周期阻滞于G0/G1期。值得注意地是，被确定为特定IMPDH2抑制剂的MMF与DOX联合使用，可显著增强治疗反应。
IMPDH2过表达与HB患者的不良预后密切相关，似乎加速了细胞周期进程。这些发现表明，IMPDH2可能是一种有价值的预后指标，也是HB的潜在治疗靶点。
本研究揭示了肝母细胞瘤（HB）组织中肌苷单磷酸脱氢酶2（IMPDH2）明显过表达，特别是与该疾病的转移和复发有关。发现IMPDH2的明显上调与HB患者的不良预后密切相关。这种过表达似乎加速了细胞周期进程，表明IMPDH2可能是HB背景下一个有前景的预后标志物和治疗靶点候选物。
