{"doi":"10.3389/fonc.2021.718408","title":"Extracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer","abstract":"BACKGROUND: Late-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. METHODS: Human 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. CONCLUSION: This 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.","journal":"Frontiers in Oncology","year":2021,"id":195193,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":330965,"name":"Nanxia Zhao","orcid":"0000-0001-8858-0975","position":1,"is_corresponding":false},{"id":405635,"name":"Jay V. Shah","orcid":null,"position":2,"is_corresponding":false},{"id":765910,"name":"Jake N. Siebert","orcid":"0000-0003-4263-6157","position":3,"is_corresponding":false},{"id":766437,"name":"Srujanesh Gunda","orcid":null,"position":4,"is_corresponding":false},{"id":766438,"name":"Berk Inan","orcid":null,"position":5,"is_corresponding":false},{"id":206102,"name":"Mijung Kwon","orcid":null,"position":6,"is_corresponding":false},{"id":381008,"name":"Steven K. Libutti","orcid":"0000-0003-2313-9809","position":7,"is_corresponding":false},{"id":330973,"name":"Prabhas V. Moghe","orcid":"0000-0002-2091-5879","position":8,"is_corresponding":false},{"id":330969,"name":"Nicola L. Francis","orcid":"0000-0002-5542-253X","position":9,"is_corresponding":false},{"id":404180,"name":"Vidya Ganapathy","orcid":"0000-0003-1275-4849","position":10,"is_corresponding":false},{"id":404172,"name":"Amber Gonda","orcid":"0000-0002-3443-120X","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:50:03.719152Z","pmid":"34868914","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}