Yildirim Nuri, Kocal Gizem Calibasi, Isik Zerrin, Saatli Bahadır, Saygili Ugur, Uysal Tugba, Ulukus Cagnur, Koyuncuoglu Meral, Ellidokuz Hulya, Basbinar Yasemin
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ege University and Department of Basic Oncology, Dokuz Eylul University. Ege Üniversitesi Hastanesi, Kadın Hastalıkları ve Doğum AD, 35100, Bornova, Izmir, Turkey.
Basic Oncology, Institute of Medical Sciences, Dokuz Eylul University, Izmir, Turkey.
Reprod Sci. 2019 Jun;26(6):794-805. doi: 10.1177/1933719118799189. Epub 2018 Sep 9.
To investigate gene expression differences and related functions between primary tumor, malignant cells in ascites, and metastatic peritoneal implant in high-grade serous ovarian cancer.
Biopsies from primary tumor, peritoneal implant, and ascites were collected from 10 patients operated primarily for high-grade, advanced-staged serous ovarian cancer. Total RNA isolation was performed from collected tissue biopsy and fluid samples, and RNA expression profile was measured. Messenger RNA expression profiles of 3 different groups were compared. Functional analyses of candidate genes were carried out by gene ontology and pathway analysis.
There were significant differences in the expression of 5 genes between primary tumor and peritoneal implant, 979 genes between primary tumor and malignant cells in ascites, and 649 genes between peritoneal implant and malignant cells in ascites. Three commonly enriched gene ontology functions between "primary tumor and malignant cells in the ascites" and "peritoneal implant and malignant cells in the ascites" were protein deubiquitination, ubiquitin-dependent protein catabolism, and apoptotic processes. All genes related to these functions belonged to gene family.
Gene expression difference between primary tumor and the peritoneal implant is not as much as the difference between primary tumor and free cells in the ascites. These results show that malignant cells in the ascites return into its genetic origin after they invade on the peritoneum. Significantly increased expression of DUB-enzyme genes, gene family, and ribosomal pathway genes in epithelial-mesenchymal transition suggests that this regulation is ubiquitin-proteasome dependent. Especially, this is the first study that offers as a potential target for epithelial-mesenchymal transition.
研究高级别浆液性卵巢癌中原发肿瘤、腹水中的恶性细胞以及腹膜转移种植灶之间的基因表达差异及相关功能。
收集10例主要接受高级别、晚期浆液性卵巢癌手术患者的原发肿瘤、腹膜种植灶及腹水的活检样本。从收集的组织活检和液体样本中提取总RNA，并测量RNA表达谱。比较3个不同组的信使RNA表达谱。通过基因本体论和通路分析对候选基因进行功能分析。
原发肿瘤与腹膜种植灶之间有5个基因表达存在显著差异，原发肿瘤与腹水中的恶性细胞之间有979个基因表达存在显著差异，腹膜种植灶与腹水中的恶性细胞之间有649个基因表达存在显著差异。“原发肿瘤与腹水中的恶性细胞”以及“腹膜种植灶与腹水中的恶性细胞”之间三个共同富集的基因本体功能是蛋白质去泛素化、泛素依赖性蛋白质分解代谢和凋亡过程。所有与这些功能相关的基因都属于基因家族。
原发肿瘤与腹膜种植灶之间的基因表达差异不如原发肿瘤与腹水中游离细胞之间的差异大。这些结果表明，腹水中的恶性细胞在侵袭腹膜后恢复到其基因起源状态。上皮-间质转化中DUB酶基因、基因家族和核糖体通路基因的表达显著增加，表明这种调节是泛素-蛋白酶体依赖性的。特别是，这是第一项将作为上皮-间质转化潜在靶点的研究。
