Nuri Yildirim1,2, Gizem Calibasi Kocal3,4, Zerrin Isik5, Bahadır Saatli6, Ugur Saygili6, Tugba Uysal3, Cagnur Ulukus7, Meral Koyuncuoglu7, Hulya Ellidokuz8, Yasemin Basbinar3,4,9. 1. 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. nuri-yildirim@hotmail.com. 2. Basic Oncology, Institute of Medical Sciences, Dokuz Eylul University, Izmir, Turkey. nuri-yildirim@hotmail.com. 3. Basic Oncology, Institute of Oncology, Dokuz Eylul University, Izmir, Turkey. 4. Personalized Medicine and Pharmacogenomics Research Center, Dokuz Eylul University, Izmir, Turkey. 5. Faculty of Engineering, Department of Computer Engineering, Dokuz Eylul University, Izmir, Turkey. 6. Faculty of Medicine, Department of Obstetrics and Gynecology, Dokuz Eylul University, Izmir, Turkey. 7. Faculty of Medicine, Department of Pathology, Dokuz Eylul University, Izmir, Turkey. 8. Department of Preventive Oncology, Institute of Oncology, Dokuz Eylul University, Izmir, Turkey. 9. Institute of Medical Sciences, Translational Oncology, Dokuz Eylul University, Izmir, Turkey.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: 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 USP17 gene family. CONCLUSION: 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, SNAR 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 USP17 as a potential target for epithelial-mesenchymal transition.
OBJECTIVES: 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. METHODS: 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. RESULTS: 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 USP17 gene family. CONCLUSION: 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, SNAR 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 USP17 as a potential target for epithelial-mesenchymal transition.
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