scholarly journals Correlation of PKM2 and CD44 Protein Expression with Poor Prognosis in Platinum-Treated Epithelial Ovarian Cancer: A Retrospective Study

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1013
Author(s):  
Chara Papadaki ◽  
Stavroula Manolakou ◽  
Eleni Lagoudaki ◽  
Spyros Pontikakis ◽  
Despo Ierodiakonou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Protein Expression ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Progression Free Survival ◽  
Free Survival ◽  
Protein Levels ◽  
Low Expression

CD44, a surface marker for cancer stem cells, interacts with PKM2, a key regulator of aerobic glycolysis, and enhances the glycolytic phenotype of cancer cells leading to antioxidant protection and macromolecules’ synthesis. To clarify the clinical importance of this “cross-talk” as a mechanism of drug resistance, we assessed the expression both of PKM2 and of CD44 in cancer cells of patients with epithelial ovarian cancer (EOC) treated with platinum-based treatment. One hundred and seventy-one patients with EOC were assessed for PKM2mRNA expression and PKM2 and CD44 proteins detection. Associations with progression-free survival (PFS) and overall survival (OS) were assessed with Kaplan–Meier and adjusted Cox regression models. PKM2mRNA and protein as well as CD44 protein were detectable in the majority of patients. Positive correlation between PKM2 and CD44 protein expression was observed (Spearman rho = 0.2, p = 0.015). When we used the median to group patients into high versus low expression, high PKM2mRNA and protein levels were significantly associated with lower progression-free survival (PFS; p = 0.003 and p = 0.002, respectively) and shorter overall survival (OS; p ≤ 0.001 and p = 0.001, respectively). However, high CD44 protein expression was significantly correlated only with shorter OS (p = 0.004). Moreover, patients with both high PKM2 and CD44 protein levels experienced shorter PFS and OS (p = 0.007 and p = 0.003, respectively) compared to patients with low expression of both proteins. Finally, higher PKM2mRNA and protein expression as well as CD44 protein expression (HR: 2.16; HR: 1.82; HR: 1.01, respectively) were independent prognostic factors for decreased median OS (mOS), whereas only PKM2 protein expression (HR: 1.95) was an independent prognostic factor for decreased median PFS (mPFS). In conclusion, PKM2 expression is a negative prognostic factor in EOC patients, but the interaction between CD44 and PKM2 that may be implicated in EOC platinum-resistance needs further investigation.

scholarly journals Identification and Analysis of Genes Associated with Epithelial Ovarian Cancer by Integrated Bioinformatics Methods

2020 ◽  
Author(s):  
Ting Gui ◽  
Chenhe Yao ◽  
Binghan Jia ◽  
Keng Shen
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Protein Interactions ◽  
Therapeutic Targets ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Ppi Network ◽  
Hub Genes ◽  
Free Survival

Abstract Background: Though considerable efforts have been made to improve the treatment of epithelial ovarian cancer (EOC), the prognosis of patients has remained poor. Identifying differentially expressed genes (DEGs) involved in EOC progression and exploiting them as novel biomarkers or therapeutic targets for EOC is highly valuable. Methods: Overlapping DEGs were screened out from three independent gene expression omnibus (GEO) datasets and subjected to Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. The protein-protein interactions (PPI) network of DEGs was constructed in the STRING database. The top 20 hub genes were selected using cytoHubba. The expression of hub genes was detected in GEPIA, Oncomine, and human protein atlas (HPA) databases. The relationship of hub genes with the pathological stage and the overall survival and progression-free survival in EOC patients was investigated using the cancer genome atlas data. Results: A total of 306 DEGs were identified, including 265 up-regulated and 41 down-regulated. Through the PPI network analysis, the top 20 genes were screened out, among which 4 hub genes were selected after literature retrieval, including CDC45, CDCA5, KIF4A, ESPL1. The four genes were up-regulated in EOC tissues and the expression of these four genes decreased gradually with the continuous progression of EOC. Survival curves illustrated that patients with a lower level of CDCA5 and ESPL1 had better overall survival and progression-free survival. Conclusions: Two hub genes, CDCA5 and ESPL1, identified as playing tumor-promotive roles, could be utilized as potential novel therapeutic targets for EOC treatment.

scholarly journals Identification and analysis of genes associated with epithelial ovarian cancer by integrated bioinformatics methods

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253136
Author(s):  
Ting Gui ◽  
Chenhe Yao ◽  
Binghan Jia ◽  
Keng Shen
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Protein Interactions ◽  
Therapeutic Targets ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Ppi Network ◽  
Hub Genes ◽  
Free Survival

Background Though considerable efforts have been made to improve the treatment of epithelial ovarian cancer (EOC), the prognosis of patients has remained poor. Identifying differentially expressed genes (DEGs) involved in EOC progression and exploiting them as novel biomarkers or therapeutic targets is of great value. Methods Overlapping DEGs were screened out from three independent gene expression omnibus (GEO) datasets and were subjected to Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. The protein-protein interactions (PPI) network of DEGs was constructed based on the STRING database. The expression of hub genes was validated in GEPIA and GEO. The relationship of hub genes expression with tumor stage and overall survival and progression-free survival of EOC patients was investigated using the cancer genome atlas data. Results A total of 306 DEGs were identified, including 265 up-regulated and 41 down-regulated. Through PPI network analysis, the top 20 genes were screened out, among which 4 hub genes, which were not researched in depth so far, were selected after literature retrieval, including CDC45, CDCA5, KIF4A, ESPL1. The four genes were up-regulated in EOC tissues compared with normal tissues, but their expression decreased gradually with the continuous progression of EOC. Survival curves illustrated that patients with a lower level of CDCA5 and ESPL1 had better overall survival and progression-free survival statistically. Conclusion Two hub genes, CDCA5 and ESPL1, identified as probably playing tumor-promotive roles, have great potential to be utilized as novel therapeutic targets for EOC treatment.

scholarly journals Comparison of the survival outcomes of laparoscopy versus laparotomy in treatment of early-stage ovarian cancer: a systematic review and meta-analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingduo Kong ◽  
Hongyi Wei ◽  
Jing Zhang ◽  
Yilin Li ◽  
Yongjun Wang
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Survival Outcomes ◽  
Free Survival ◽  
Review Manager ◽  
Early Stage Ovarian Cancer

Abstract Background Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC. Methods According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2). Results A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008). Conclusions Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.

Addition of bevacizumab to weekly paclitaxel significantly improves progression-free survival in heavily pretreated recurrent epithelial ovarian cancer

2011 ◽  
Vol 121 (2) ◽  
pp. 269-272 ◽  
Author(s):  
David M. O'Malley ◽  
Debra L. Richardson ◽  
Patrick S. Rheaume ◽  
Ritu Salani ◽  
Eric L. Eisenhauer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Progression Free Survival ◽  
Weekly Paclitaxel ◽  
Free Survival ◽  
Heavily Pretreated

Prognostic Relevance of Celiac Lymph Node Involvement in Ovarian Cancer

2014 ◽  
Vol 24 (1) ◽  
pp. 48-53 ◽  
Author(s):  
Alejandra Martínez ◽  
Cristophe Pomel ◽  
Thomas Filleron ◽  
Marjolein De Cuypere ◽  
Eliane Mery ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Oncologic Outcome ◽  
Progression Free Survival ◽  
Disease Spread ◽  
Short Term ◽  
Free Survival ◽  
Increased Risk

ObjectiveThe aim of the study was to report on the oncologic outcome of the disease spread to celiac lymph nodes (CLNs) in advanced-stage ovarian cancer patients.MethodsAll patients who had CLN resection as part of their cytoreductive surgery for epithelial ovarian, fallopian, or primary peritoneal cancer were identified. Patient demographic data with particular emphasis on operative records to detail the extent and distribution of the disease spread, lymphadenectomy procedures, pathologic data, and follow-up data were included.ResultsThe median follow-up was 26.3 months. The median overall survival values in the group with positive CLNs and in the group with negative CLNs were 26.9 months and 40.04 months, respectively. The median progression-free survival values in the group with metastatic CLNs and in the group with negative CLNs were 8.8 months and 20.24 months, respectively (P = 0.053). Positive CLNs were associated with progression during or within 6 months after the completion of chemotherapy (P = 0.0044). Tumor burden and extensive disease distribution were significantly associated with poor progression-free survival, short-term progression, and overall survival. In multivariate analysis, only the CLN status was independently associated with short-term progression.ConclusionsDisease in the CLN is a marker of disease severity, which is associated to a high-risk group of patients with presumed adverse tumor biology, increased risk of lymph node progression, and worst oncologic outcome.

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