Hishinuma Eiji, Shigeta Shogo, Matsukawa Naomi, Okamura Yasunobu, Motoike Ikuko N, Minato Takamichi, Shibuya Yusuke, Yasuda Jun, Kinoshita Kengo, Koshiba Seizo, Shimada Muneaki
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.
Int J Mol Sci. 2025 Jun 6;26(12):5435. doi: 10.3390/ijms26125435.
Epithelial ovarian cancer (EOC) is diagnosed at an advanced stage in over half of the patients and its prognosis remains unfavorable. CA125, one of the most frequent positive tumor markers in patients with EOC, has certain limitations. Therefore, more accurate clinical biomarkers are needed. Liquid biopsy with cancer related molecules, such as circulating tumor DNA, is a new option for cancer diagnosis and prognosis. We explored the potential of plasma metabolomic and proteomic analyses as novel monitoring methods for the patients with EOC. Of seven patients, six experienced disease recurrence or progression. CA125 plasma measurements were conducted for disease monitoring. Plasma metabolome and proteome analyses were performed using liquid chromatography-tandem mass spectrometry. Ten and four metabolome indicators were significantly increased and decreased in association with chemotherapeutic resistance, respectively. In addition, thirty-seven and nine proteins displayed high and low levels associated with chemotherapeutic resistance, respectively. Several metabolome pathways and protein concentrations corresponded to the clinical course of each patient. This pilot study suggested the potential of the assessment of metabolome and proteome analysis as a useful tool for developing novel monitoring biomarkers for patients with recurrent EOC.
上皮性卵巢癌（EOC）在超过半数的患者中被诊断为晚期，其预后仍然不佳。CA125是EOC患者中最常见的阳性肿瘤标志物之一，存在一定局限性。因此，需要更准确的临床生物标志物。对与癌症相关的分子（如循环肿瘤DNA）进行液体活检是癌症诊断和预后评估的一种新选择。我们探索了血浆代谢组学和蛋白质组学分析作为EOC患者新型监测方法的潜力。7名患者中有6名经历了疾病复发或进展。通过检测CA125血浆水平进行疾病监测。采用液相色谱-串联质谱法进行血浆代谢组和蛋白质组分析。分别有10个和4个代谢组指标与化疗耐药相关且显著升高和降低。此外，分别有37种和9种蛋白质与化疗耐药相关且呈现高水平和低水平。几种代谢组途径和蛋白质浓度与每位患者的临床病程相符。这项初步研究表明，代谢组和蛋白质组分析评估作为开发复发性EOC患者新型监测生物标志物的有用工具具有潜力。
