Abstract A32: Single-cell RNA-seq analysis of primary tumor and corresponding metastatic lesion in high-grade serous ovarian cancer

Author(s):  
Andrew Shih ◽  
Andrew Menzin ◽  
Jill Whyte ◽  
John Lovecchio ◽  
Anthony Liew ◽  
...  
Author(s):  
Slavomir Krajnak ◽  
Jörg Jäkel ◽  
Katharina Anić ◽  
Roxana Schwab ◽  
Marcus Schmidt ◽  
...  

Abstract Purpose Integrins may be involved in the metastatic spread of high-grade serous ovarian cancer (HGSOC) which determines the therapeutical approach and prognosis. We investigated the integrin expression in primary tumor and metastases of advanced HGSOC. Methods The expression of integrin α2, α4, α5, α6, and β1 was assessed by immunostaining in tumor samples of the ovary, omentum, and peritoneum of each patient. Differences in integrin expression among tumor localizations and their association with clinicopathological parameters were examined by Fisher’s exact test. The impact of integrin expression on progression-free survival (PFS) and overall survival (OS) was examined by Cox regression and Kaplan–Meier analyses. Results Hundred and thirteen tumor samples of 40 HGSOC patients were examined. The expression of the integrins did not differ between the three tumor localizations (all p values > 0.05) with the exception of high expression of integrin α4 in primary tumor and omentum (52.5% versus 47.5%, p = 0.008) and primary tumor and peritoneum (52.5% versus 47.5%, p = 0.050). High expression of integrin α4 in peritoneum was associated with poorer PFS (HR 2.02 95% CI 1.01–4.05, p = 0.047), younger age (p = 0.047), and death (p = 0.046). Median PFS in patients with high expression of integrin α4 was 13.00 months, whereas median PFS in patients without high expression of integrin α4 was 21.00 months (p = 0.040). Expression of other integrins did not correlate with PFS or OS. Conclusion Expression of integrin α4 may be altered during the metastatic spread of HGSOC and affect prognosis, whereas expression of integrin α2, α5, α6, and β1 did not reveal any prognostic value.


2018 ◽  
Vol 26 (6) ◽  
pp. 794-805 ◽  
Author(s):  
Nuri Yildirim ◽  
Gizem Calibasi Kocal ◽  
Zerrin Isik ◽  
Bahadır Saatli ◽  
Ugur Saygili ◽  
...  

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.


2017 ◽  
Author(s):  
Anniina Farkkila ◽  
Kaiyang Zhang ◽  
Katja Kaipio ◽  
Tarja Lamminen ◽  
Rainer Lehtonen ◽  
...  

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