Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Sci Rep. 2024 Jan 2;14(1):15. doi: 10.1038/s41598-023-51009-z.
Metabolic alterations play an essential role in ovarian carcinogenesis. The flexibility of mitochondrial functions facilitates cellular adaptation to the tough environment associated with carcinogenesis. An understanding of the differences in mitochondrial functions in normal ovaries and cancers could provide a basis for further exploration of future mitochondria-based screening, diagnosis, prognostic prediction, and targeted therapy for epithelial ovarian cancers. The main objective of this study was to assess mitochondrial function profiles measured from PBMCs and ovarian tissues of epithelial ovarian cancers in comparison with normal ovaries. A total of 36 patients were recruited for the study, all of whom underwent primary surgical treatment for malignant epithelial ovarian neoplasm. Of these, 20 patients were in the early stage and 16 patients were in the advanced stage. Additionally, 21 patients who had pelvic surgery for benign gynecologic conditions, with normal ovaries incidentally removed, were recruited as controls. At the time of surgery, a blood sample was collected from each participant for PBMC isolation, and ovarian tissue was retained for molecular studies. These studies included the examination of oxidative stress, mitochondrial mass, mitochondrial respiration, mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP) changes, and mitochondrial swelling. Clinical and histopathological data were also collected and compared between different stages of epithelial ovarian cancers: early-stage (group 1), advanced-stage (group 2), and normal ovaries (group 3). The levels of cellular oxidative stress, mitochondrial mass, and mitochondrial biogenesis in the peripheral blood mononuclear cells (PBMCs) of participants with ovarian cancer were significantly lower than those of the control group. However, the mitochondrial respiratory parameters measured from the PBMCs were similar across all three groups. Furthermore, mitochondrial membrane depolarization and mitochondrial swelling were observed in ovarian tissues of both early-stage and advanced-stage cancer groups. We demonstrated the dynamic nature of mitochondrial ROS production, biogenesis, and respiratory function in response to epithelial ovarian carcinogenesis. The flexibility of mitochondrial functions under diverse conditions may make it a challenging therapeutic target for ovarian cancer.
代谢改变在卵巢癌发生中起着重要作用。线粒体功能的灵活性促进了细胞对与癌变相关的恶劣环境的适应。了解正常卵巢和癌症中线粒体功能的差异，可以为进一步探索基于线粒体的上皮性卵巢癌筛查、诊断、预后预测和靶向治疗提供基础。本研究的主要目的是评估从上皮性卵巢癌患者的 PBMC 和卵巢组织中测量的线粒体功能谱，并与正常卵巢进行比较。共招募了 36 名患者进行本研究，所有患者均因恶性上皮性卵巢肿瘤接受了初次手术治疗。其中，20 例为早期，16 例为晚期。此外，还招募了 21 例因良性妇科疾病行盆腔手术且意外切除正常卵巢的患者作为对照组。在手术时，从每位参与者采集一份血样用于 PBMC 分离，并保留卵巢组织进行分子研究。这些研究包括氧化应激、线粒体质量、线粒体呼吸、线粒体活性氧（ROS）、线粒体膜电位（MMP）变化和线粒体肿胀的检查。还收集了临床和组织病理学数据，并在不同分期的上皮性卵巢癌之间进行了比较：早期（组 1）、晚期（组 2）和正常卵巢（组 3）。与对照组相比，卵巢癌患者外周血单个核细胞（PBMC）中的细胞氧化应激、线粒体质量和线粒体生物发生水平明显降低。然而，从 PBMC 测量的线粒体呼吸参数在三组之间相似。此外，早期和晚期癌症组的卵巢组织中均观察到线粒体膜去极化和线粒体肿胀。我们证明了线粒体 ROS 产生、生物发生和呼吸功能对上皮性卵巢癌发生的动态变化。在不同条件下，线粒体功能的灵活性可能使其成为卵巢癌治疗的挑战性靶点。
