Advanced Research Center for Innovations in Next Generation Medicine, Tohoku University, Sendai 980-8573, Japan.
Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Japan.
Toxins (Basel). 2021 Jun 30;13(7):461. doi: 10.3390/toxins13070461.
Epithelial ovarian cancer (EOC) is a fatal gynecologic cancer, and its poor prognosis is mainly due to delayed diagnosis. Therefore, biomarker identification and prognosis prediction are crucial in EOC. Altered cell metabolism is a characteristic feature of cancers, and metabolomics reflects an individual's current phenotype. In particular, plasma metabolome analyses can be useful for biomarker identification. In this study, we analyzed 624 metabolites, including uremic toxins (UTx) in plasma derived from 80 patients with EOC using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Compared with the healthy control, we detected 77 significantly increased metabolites and 114 significantly decreased metabolites in EOC patients. Especially, decreased concentrations of lysophosphatidylcholines and phosphatidylcholines and increased concentrations of triglycerides were observed, indicating a metabolic profile characteristic of EOC patients. After calculating the parameters of each metabolic index, we found that higher ratios of kynurenine to tryptophan correlates with worse prognosis in EOC patients. Kynurenine, one of the UTx, can affect the prognosis of EOC. Our results demonstrated that plasma metabolome analysis is useful not only for the diagnosis of EOC, but also for predicting prognosis with the variation of UTx and evaluating response to chemotherapy.
上皮性卵巢癌(EOC)是一种致命的妇科癌症,其预后不良主要归因于诊断延误。因此,生物标志物的识别和预后预测在 EOC 中至关重要。癌细胞的代谢改变是癌症的一个特征,代谢组学反映了个体当前的表型。特别是,血浆代谢组分析可用于生物标志物的识别。在本研究中,我们使用超高效液相色谱-串联质谱法(UHPLC-MS/MS)分析了 80 名 EOC 患者血浆中的 624 种代谢物,包括尿毒症毒素(UTx)。与健康对照组相比,我们在 EOC 患者中检测到 77 种明显增加的代谢物和 114 种明显减少的代谢物。特别是,发现了溶血磷脂酰胆碱和磷脂酰胆碱浓度降低,甘油三酯浓度升高,这表明 EOC 患者存在代谢特征。在计算每个代谢指标的参数后,我们发现色氨酸与犬尿氨酸的比值越高,EOC 患者的预后越差。犬尿氨酸是 UTx 之一,它可以影响 EOC 的预后。我们的研究结果表明,血浆代谢组分析不仅有助于 EOC 的诊断,还可以通过 UTx 的变化预测预后,并评估对化疗的反应。