Extracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Amber Gonda, Nanxia Zhao, Jay V. Shah, Jake N. Siebert, Srujanesh Gunda, Berk Inan, Mijung Kwon, Steven K. Libutti, Prabhas V. Moghe, Nicola L. Francis, Vidya Ganapathy
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	extracellular vesicle exosome gene signatures metastasis ovarian cancer 2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/4f7534a0ee9e4be0952e2d43d5e9bfdc
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4f7534a0ee9e4be0952e2d43d5e9bfdc
record_format	dspace
spelling	oai:doaj.org-article:4f7534a0ee9e4be0952e2d43d5e9bfdc2021-11-18T09:22:55ZExtracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer2234-943X10.3389/fonc.2021.718408https://doaj.org/article/4f7534a0ee9e4be0952e2d43d5e9bfdc2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.718408/fullhttps://doaj.org/toc/2234-943XBackgroundLate-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.Amber GondaNanxia ZhaoJay V. ShahJake N. SiebertJake N. SiebertSrujanesh GundaBerk InanMijung KwonSteven K. LibuttiPrabhas V. MoghePrabhas V. MogheNicola L. FrancisVidya GanapathyFrontiers Media S.A.articleextracellular vesicleexosomegene signaturesmetastasisovarian cancer 2Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	extracellular vesicle exosome gene signatures metastasis ovarian cancer 2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	extracellular vesicle exosome gene signatures metastasis ovarian cancer 2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Amber Gonda Nanxia Zhao Jay V. Shah Jake N. Siebert Jake N. Siebert Srujanesh Gunda Berk Inan Mijung Kwon Steven K. Libutti Prabhas V. Moghe Prabhas V. Moghe Nicola L. Francis Vidya Ganapathy Extracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer
description	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.
format	article
author	Amber Gonda Nanxia Zhao Jay V. Shah Jake N. Siebert Jake N. Siebert Srujanesh Gunda Berk Inan Mijung Kwon Steven K. Libutti Prabhas V. Moghe Prabhas V. Moghe Nicola L. Francis Vidya Ganapathy
author_facet	Amber Gonda Nanxia Zhao Jay V. Shah Jake N. Siebert Jake N. Siebert Srujanesh Gunda Berk Inan Mijung Kwon Steven K. Libutti Prabhas V. Moghe Prabhas V. Moghe Nicola L. Francis Vidya Ganapathy
author_sort	Amber Gonda
title	Extracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer
title_short	Extracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer
title_full	Extracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer
title_fullStr	Extracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer
title_full_unstemmed	Extracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer
title_sort	extracellular vesicle molecular signatures characterize metastatic dynamicity in ovarian cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4f7534a0ee9e4be0952e2d43d5e9bfdc
work_keys_str_mv	AT ambergonda extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT nanxiazhao extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT jayvshah extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT jakensiebert extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT jakensiebert extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT srujaneshgunda extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT berkinan extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT mijungkwon extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT stevenklibutti extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT prabhasvmoghe extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT prabhasvmoghe extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT nicolalfrancis extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer AT vidyaganapathy extracellularvesiclemolecularsignaturescharacterizemetastaticdynamicityinovariancancer
_version_	1718420902049218560

Extracellular Vesicle Molecular Signatures Characterize Metastatic Dynamicity in Ovarian Cancer

Ejemplares similares