scholarly journals Extracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Amber Gonda ◽  
Nanxia Zhao ◽  
Jay V. Shah ◽  
Jake N. Siebert ◽  
Srujanesh Gunda ◽  
...  

BackgroundLate-stage diagnosis of ovarian cancer, a disease that originates in the ovaries and spreads to the peritoneal cavity, lowers 5-year survival rate from 90% to 30%. Early screening tools that can: i) detect with high specificity and sensitivity before conventional tools such as transvaginal ultrasound and CA-125, ii) use non-invasive sampling methods and iii) longitudinally significantly increase survival rates in ovarian cancer are needed. Studies that employ blood-based screening tools using circulating tumor-cells, -DNA, and most recently tumor-derived small extracellular vesicles (sEVs) have shown promise in non-invasive detection of cancer before standard of care. Our findings in this study show the promise of a sEV-derived signature as a non-invasive longitudinal screening tool in ovarian cancer.MethodsHuman serum samples as well as plasma and ascites from a mouse model of ovarian cancer were collected at various disease stages. Small extracellular vesicles (sEVs) were extracted using a commercially available kit. RNA was isolated from lysed sEVs, and quantitative RT-PCR was performed to identify specific metastatic gene expression.ConclusionThis paper highlights the potential of sEVs in monitoring ovarian cancer progression and metastatic development. We identified a 7-gene panel in sEVs derived from plasma, serum, and ascites that overlapped with an established metastatic ovarian carcinoma signature. We found the 7-gene panel to be differentially expressed with tumor development and metastatic spread in a mouse model of ovarian cancer. The most notable finding was a significant change in the ascites-derived sEV gene signature that overlapped with that of the plasma-derived sEV signature at varying stages of disease progression. While there were quantifiable changes in genes from the 7-gene panel in serum-derived sEVs from ovarian cancer patients, we were unable to establish a definitive signature due to low sample number. Taken together our findings show that differential expression of metastatic genes derived from circulating sEVs present a minimally invasive screening tool for ovarian cancer detection and longitudinal monitoring of molecular changes associated with progression and metastatic spread.

2021 ◽  
Author(s):  
Amber Gonda ◽  
Nanxia Zhao ◽  
Jay V. Shah ◽  
Jake N. Siebert ◽  
Srujanesh Gunda ◽  
...  

AbstractLate-stage diagnosis of ovarian cancer drastically lowers 5-year survival rate from 90% to 30%. Early screening tools that use non-invasive sampling methods combined with high specificity and sensitivity can significantly increase survival. Emerging research employing blood-based screening tools have shown promise in non-invasive detection of cancer. Our findings in this study show the potential of a small extracellular vesicle (sEV)-derived signature as a non-invasive longitudinal screening tool in ovarian cancer. We identified a 7-gene panel in these sEVs that overlapped with an established tissue-derived metastatic ovarian carcinoma signature. We found the 7-gene panel to be differentially expressed with tumor development and metastatic spread. While there were quantifiable changes in genes from the 7-gene panel in plasma-derived sEVs from ovarian cancer patients, we were unable to establish a definitive signature due to low sample number. The most notable finding was a significant change in the ascites-derived sEV gene signature that overlapped with that of the plasma-derived sEV signature at varying stages of disease progression. Taken together our findings show that differential expression of metastatic genes derived from circulating sEVs present a minimally invasive screening tool for ovarian cancer detection and longitudinal monitoring of molecular changes associated with progression and metastatic spread.


2015 ◽  
Vol 12 (1) ◽  
pp. 55-62
Author(s):  
Baghdad Science Journal

Epithelial ovarian cancer is the leading cause of cancer deaths in women. To date, an effective screening tool for ovarian cancer has not been identified Several clinical and biological factors including serum cancer antigen 125 (CA- 125) have been assessed for prognostic and predictive relevance CA-125 is an epithelial marker derived from coelomic epithelium. It is elevated in 90% of advanced ovarian cancers and in 50% of early ovarian cancers while 20% of ovarian cancers have low or no expression of CA- 125 CA-125 concentrations were measured by Mini Vidas test (VIDAS CA125 II / BIOMERIEUX / France). The median CA-125 levels were significantly higher in the sera of ovarian cancer patients than in those with benign tumors and in healthy controls. However in correlation with stages the results showed that Patients with stage II have highly significant differences in level of serum CA125 compare with stage I in and stage III.CA125 showed low sensitivity to detect stage I carcinoma of the ovary which limits its value as an initial screening tool therefore combining of CA125 with other markers might enable improved early detection of ovarian cancer as compared with use of this marker alone.


2012 ◽  
Author(s):  
Rao V. Papineni ◽  
Vinicius Craveiro ◽  
John Pizzonia ◽  
Jennie Holmberg ◽  
Gil Mor

1995 ◽  
Vol 13 (3) ◽  
pp. 783-793 ◽  
Author(s):  
S E Mackey ◽  
W T Creasman

PURPOSE To review potential screening tools of early ovarian cancer and the associated risk factors for the development of ovarian carcinoma. DESIGN AND RESULTS A review of pertinent literature was conducted, restricted to English-language published reports, book chapters, and articles. The value of serum tumor markers, particularly CA 125, ultrasound, transabdominal and transvaginal ultrasonography, and transvaginal color Doppler imaging as screening tools for ovarian cancer was assessed. CONCLUSION Based on the literature, a large-scale long-term study that compares the mortality rates of a screened versus unscreened patient population is required before the efficacy of any screening method can be determined definitively.


2020 ◽  
Vol 11 (5) ◽  
pp. 54-60
Author(s):  
Apurba Mandal ◽  
Shibram Chattopadhyay ◽  
Sushanta Mondal ◽  
Arunava Biswas

Background: Adnexal mass is a common presentation in today’s gynecological practice. The incidence of ovarian cancer is increasing day by day and diagnosis is often difficult to be made pre operatively with inadequate surgical exploration is a regular occurrence. Aims and Objectives: To assess and validate the importance of RMI-3 score as pre-operative diagnostic tool of differentiating benign from malignant adnexal mass for starting first line therapy of ovarian cancer and to find out the incidences of ovarian malignancy among study population. Material and Methods: The study was conducted in the Department of Gynecology and Obstetrics on (n=115) patients attending GOPD and indoor with adnexal mass fulfilling the inclusion and exclusion criteria using purposive sampling technique. All the selected cases underwent ultrasonography and serum CA- 125 level estimation necessary for calculating RMI score. A score of >200 was taken as suggestive of malignancy and confirmatory diagnosis was performed by histopathological examination obtained from staging laparotomy of adnexal mass. The individual scores were then correlated with final outcomes with statistical analyses. Results: The study revealed benign ovarian tumors are more under 50 years (78.46%) and patients with normal BMI are diagnosed with maximum of malignancy (n = 28). History of tubal ligation carried less risk of malignancy (p<0.0001). Histologically malignant tumors found mostly in 71.4% postmenopausal group whereas 94.1% benign pathology were present in perimenopausal group and there is no association found between parity and histopathology (p=0.058). Bilateral (p=0.013), multilocular (p=0.000) tumors with solid areas (p<0.0001) and thick papillary projections (p<0.0001) had statistically significant association with malignant lesions. RMI score (>200) had more efficacy than serum CA-125 level (>46) in differentiating malignant lesions from benign one in terms of specificity (96% vs 83.87%) and positive predictive value (95% vs 79.17%). Conclusions: RMI-3 score is a simple, reliable and effective tool in differentiating benign from malignant adnexal masses thereby help in quick referral and management of cases with increase chances of survival of the patients.


2020 ◽  
Vol 21 ◽  
Author(s):  
Yin-xue Wang ◽  
Yi-xiang Wang ◽  
Yi-ke Li ◽  
Shi-yan Tu ◽  
Yi-qing Wang

: Ovarian cancer (OC) is one of the deadliest gynecological malignancy. Epithelial ovarian cancer (EOC) is its most common form. OC has both a poor prognosis and a high mortality rate due to the difficulties of early diagnosis, the limitation of current treatment and resistance to chemotherapy. Extracellular vesicles is a heterogeneous group of cellderived submicron vesicles which can be detected in body fluids, and it can be classified into three main types including exosomes, micro-vesicles, and apoptotic bodies. Cancer cells can produce more EVs than healthy cells. Moreover, the contents of these EVs have been found distinct from each other. It has been considered that EVs shedding from tumor cells may be implicated in clinical applications. Such as a tool for tumor diagnosis, prognosis and potential treatment of certain cancers. In this review, we provide a brief description of EVs in diagnosis, prognosis, treatment, drug-resistant of OC. Cancer-related EVs show powerful influences on tumors by various biological mechanisms. However, the contents mentioned above remain in the laboratory stage and there is a lack of large-scale clinical trials, and the maturity of the purification and detection methods is a constraint. In addition, amplification of oncogenes on ecDNA is remarkably prevalent in cancer, it may be possible that ecDNA can be encapsulated in EVs and thus detected by us. In summary, much more research on EVs needs to be perform to reveal breakthroughs in OC and to accelerate the process of its application on clinic.


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