scholarly journals Role of integrins in the metastatic spread of high-grade serous ovarian cancer

2021 ◽  
Author(s):  
Slavomir Krajnak ◽  
Jörg Jäkel ◽  
Katharina Anić ◽  
Roxana Schwab ◽  
Marcus Schmidt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Tumor ◽  
High Expression ◽  
Metastatic Spread ◽  
Clinicopathological Parameters ◽  
Integrin Expression ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Integrin Α4 ◽  
Integrin Α2

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.

Ubiquitin–Proteasome Axis, Especially Ubiquitin-Specific Protease-17 (USP17) Gene Family, is a Potential Target for Epithelial–Mesenchymal Transition in High-Grade Serous Ovarian Cancer

2018 ◽  
Vol 26 (6) ◽  
pp. 794-805 ◽  
Author(s):  
Nuri Yildirim ◽  
Gizem Calibasi Kocal ◽  
Zerrin Isik ◽  
Bahadır Saatli ◽  
Ugur Saygili ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gene Family ◽  
Primary Tumor ◽  
Epithelial Mesenchymal Transition ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Malignant Cells ◽  
Mesenchymal Transition ◽  
Peritoneal Implant ◽  
Ubiquitin Proteasome

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.

scholarly journals Characterization of Candidate Factors Associated With the Metastasis and Progression of High Grade Serous Ovarian Cancer

2021 ◽  
Author(s):  
Huiping Liu ◽  
Ling Zhou ◽  
Hongyan Cheng ◽  
Shang Wang ◽  
Wenqing Luan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Tumor ◽  
Gynecological Cancer ◽  
Wnt Signaling Pathway ◽  
The Cancer Genome Atlas ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Hub Genes ◽  
Bioinformatics Analyses ◽  
Factors Associated

Abstract Background. High grade serous ovarian cancer (HGSOC) is the highest cause of gynecological cancer-related mortality due to the extremely metastatic nature of this disease. The goal of this study is to explore and evaluate the profiles and characteristics of candidate factors associated with metastasis and progression of HGSOC.Methods. Transcriptomic data of HGSOC patients’ samples collected from the primary tumor and matched omental metastatic tumor were obtained from three independent studies in the NCBI GEO database. Genes significantly up-regulated and down-regulated were selected to evaluate the effects to prognosis and progression of ovarian cancer using data of ovarian cancer patients from The Cancer Genome Atlas (TCGA) database. Enrichment analysis for biological processes and pathways was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis. Furthermore, the hub genes immune landscapes were estimated by Tumor Immune Estimation Resource (TIMER) database.Results. 14 candidate genes included ADIPOQ, ALPK2, BARX1, CD37, CNR2, COL5A3, FABP4, FAP, GPR68, ITGBL1, MOXD1, PODNL1, SFRP2 and TRAF3IP3 were selected as up-regulated genes in metastatic tumors in every database while CADPS, GATA4, STAR and TSPAN8 were down-regulated. These 14 genes were significantly enriched for negative regulation of Wnt signaling pathway, fat cell differentiation, extracellular matrix organization. Finally, ALPK2, FAP, SFRP2 and GATA4, STAR, TSPAN8 were selected as hub genes that were found to be significantly associated with the survival and recurrence. All hub genes were correlated with several types of tumor microenvironmental cells infiltration significantly, especially for cancer associated fibroblasts and NK cells.Conclusions. This study indicates that screening for differentially expressed genes and pathways in HGSOC primary tumor and matched metastasis tumor using integrated bioinformatics analyses. In sum, we identify six hub genes correlated with the progression of HGSOC in our study, which might provide effective targets to predict prognosis and provide novel insights into immune-based therapy strategies of HGSOC well.

scholarly journals 317 Role of integrins in the metastatic spread of high-grade serous ovarian cancer

2021 ◽  
Author(s):  
S Krajnak ◽  
J Jäkel ◽  
K Anic ◽  
AS Heimes ◽  
V Linz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Metastatic Spread ◽  
High Grade ◽  
Serous Ovarian Cancer
Sign in / Sign up

Export Citation Format

Share Document