Department of Gynecology and Gynecological Oncology, Medical University of Bialystok, Marii Skłodowskiej-Curie 24A Street, 15-276 Bialystok, Poland.
Department of Physiology, Medical University of Bialystok, Mickiewicza 2C Street, 15-222 Bialystok, Poland.
Int J Mol Sci. 2022 Aug 11;23(16):8968. doi: 10.3390/ijms23168968.
Ovarian cancer is a non-homogenous malignancy. High-grade serous carcinoma (HGSC) is the most common subtype, and its drug resistance mechanisms remain unclear. Despite the advantages of modern pharmacotherapy, high-grade ovarian cancer is associated with a poor prognosis and research into targeted therapies is in progress. The aim of the study was to assess the dominant energy substrate transport mechanism in ovarian cancer cells and to verify whether genomic aberrations could predict clinical outcomes using the Cancer Genome Atlas (TCGA) dataset. Total RNA was extracted from HGSC frozen tissues, and the expression of selected genes was compared to respective controls. , , and genes were significantly overexpressed in carcinomas compared with controls, while expression of , , , , and was decreased. No differences were found in , , and . The transcript content of mitochondrial genes such as , and was similar between groups, while the level declined in ovarian cancer. Additionally, the level was reduced and was elevated in cancer tissue from patients with 'small' primary tumor and omental invasion accompanied by ascites as compared to patients that exhibited greater tendencies to metastasize to lymph nodes with clear omentum. Based on TCGA, higher and and lower expression indicated poorer overall survival in patients with ovarian cancer. In conclusion, the presented data show that there is no exclusive energy substrate in HGSC. However, this study indicates the advantage of glucose and lactate transport over fatty acids, thereby suggesting potential therapeutic intervention targets to impede ovarian cancer growth.
卵巢癌是一种非同质恶性肿瘤。高级别浆液性癌（HGSC）是最常见的亚型，其耐药机制尚不清楚。尽管现代药物治疗有优势，但高级别卵巢癌预后不良，目前正在进行靶向治疗的研究。本研究旨在评估卵巢癌细胞中主要能量底物转运机制，并使用癌症基因组图谱（TCGA）数据集验证基因组异常是否可以预测临床结果。从 HGSC 冷冻组织中提取总 RNA，并将选定基因的表达与各自的对照进行比较。与对照组相比， 、 、 和 基因在癌组织中显著过表达，而 、 、 、 和 的表达降低。 、 、 和 之间没有差异。线粒体基因如 、 和 的转录物含量在各组之间相似，而卵巢癌中的 水平下降。此外，与表现出更大淋巴结转移倾向且大网膜清晰的患者相比，在原发性肿瘤较小且伴有腹水的网膜侵犯患者的癌组织中， 水平降低， 水平升高。基于 TCGA，卵巢癌患者中 和 表达较高且 表达较低，总生存期较差。总之，所提供的数据表明 HGSC 中没有独特的能量底物。然而，本研究表明葡萄糖和乳酸转运的优势超过脂肪酸，从而为阻碍卵巢癌生长提供了潜在的治疗干预靶点。
