未经证实:骨肉瘤是最常见的原发性恶性骨肿瘤,原发性转移患者约占所有骨肉瘤患者的25%,然而,他们的5年OS仍然低于30%。胆红素在氧化应激相关事件中起关键作用,包括恶性肿瘤,使其血清水平的调节成为一种潜在的抗肿瘤策略。在这里,我们调查了骨肉瘤预后与血清TBIL水平的关系,IBIL和DBIL,并进一步探讨胆红素影响肿瘤侵袭和迁移的机制。
UNASSIGNED:基于所确定的最佳截断值和AUC绘制ROC曲线以评估存活条件。然后,卡普兰-迈耶曲线,以及Cox比例风险模型,用于生存分析。使用qRT-PCR检查IBIL对骨肉瘤细胞恶性特性的抑制作用,transwell分析,西方印迹,和流式细胞术。
未经授权:我们发现,与骨肉瘤患者术前IBIL较高(>8.9μmol/L),IBIL低(≤8.9μmol/L)者的OS和PFS较短。如Cox比例风险模型所示,术前IBIL作为总的和性别分层的骨肉瘤患者OS和PFS的独立预后因素(均P<0.05)。体外实验进一步证实,IBIL抑制PI3K/AKT磷酸化,通过减少细胞内ROS下调MMP-2表达,从而减少骨肉瘤细胞的侵袭。
UNASSIGNED:IBIL可作为骨肉瘤患者的独立预后预测因子。IBIL通过抑制细胞内ROS抑制PI3K/AKT/MMP-2通路,从而损害骨肉瘤细胞的侵袭,从而抑制其转移潜力。
UNASSIGNED: Osteosarcoma is most prevalently found primary malignant bone tumors, with primary metastatic patients accounting for approximately 25% of all osteosarcoma patients, yet their 5-year OS remains below 30%. Bilirubin plays a key role in oxidative stress-associated events, including malignancies, making the regulation of its serum levels a potential anti-tumor strategy. Herein, we investigated the association of osteosarcoma prognosis with serum levels of TBIL, IBIL and DBIL, and further explored the mechanisms by which bilirubin affects tumor invasion and migration.
UNASSIGNED: ROC curve was plotted to assess survival conditions based on the determined optimal cut-off values and the AUC. Then, Kaplan-Meier curves, along with Cox proportional hazards model, was applied for survival analysis. Inhibitory function of IBIL on the malignant properties of osteosarcoma cells was examined using the qRT-PCR, transwell assays, western blotting, and flow cytometry.
UNASSIGNED: We found that, versus osteosarcoma patients with pre-operative higher IBIL (>8.9 μmol/L), those with low IBIL (≤8.9 μmol/L) had shorter OS and PFS. As indicated by the Cox proportional hazards model, pre-operative IBIL functioned as an independent prognostic factor for OS and PFS in total and gender-stratified osteosarcoma patients (P < 0.05 for all). In vitro experiments further confirmed that IBIL inhibits PI3K/AKT phosphorylation and downregulates MMP-2 expression via reducing intracellular ROS, thereby decreasing the invasion of osteosarcoma cells.
UNASSIGNED: IBIL may serve as an independent prognostic predictor for osteosarcoma patients. IBIL impairs invasion of osteosarcoma cells through repressing the PI3K/AKT/MMP-2 pathway by suppressing intracellular ROS, thus inhibiting its metastatic potential.