Abstract
Late-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.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- ACTB
- actin-beta
- AEBP1
- AE Binding Protein
- ANOVA
- analysis of variance
- COL5A1
- collagen type V alpha 1 chain
- COL11A1
- collagen type XI alpha 1 chain
- ECM
- extracellular matrix
- EMT
- epithelial-mesenchymal transition
- EV
- extracellular vesicle
- FDA
- United States Food and Drug Administration
- LOX
- lysyl oxidase
- NECTIN4
- nectin cell adhesion molecule 4
- NTA
- nanoparticle tracking analysis
- POSTN
- periostin
- PBS
- phosphate-buffered saline
- RFP
- red fluorescence protein
- RT-PCR
- real-time polymerase chain reaction
- sEV
- small extracellular vesicle
- SNAI1
- snail family transcriptional repressor 1
- TCGA
- the Cancer Genome Atlas
- THBS1
- thrombospondin 1
- TIMP3
- tissue inhibitor of metalloproteinase 3
- TME
- tumor microenvironment
- TNM
- tumor-node-metastasis staging