Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy
Extracellular vesicles (EVs) are g7aining increased attention as carriers of cancer-derived molecules for liquid biopsies. Here, we studied the dynamics of EV levels in the plasma of breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC) and explored the relevance of their RNA cargo f...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1005812/full |
| _version_ | 1811234829864271872 |
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| author | Lilite Sadovska Pawel Zayakin Kristaps Eglītis Edgars Endzeliņš Ilze Radoviča-Spalviņa Elīza Avotiņa Jānis Auders Laura Keiša Inta Liepniece-Karele Inta Liepniece-Karele Mārcis Leja Jānis Eglītis Jānis Eglītis Aija Linē |
| author_facet | Lilite Sadovska Pawel Zayakin Kristaps Eglītis Edgars Endzeliņš Ilze Radoviča-Spalviņa Elīza Avotiņa Jānis Auders Laura Keiša Inta Liepniece-Karele Inta Liepniece-Karele Mārcis Leja Jānis Eglītis Jānis Eglītis Aija Linē |
| author_sort | Lilite Sadovska |
| collection | DOAJ |
| description | Extracellular vesicles (EVs) are g7aining increased attention as carriers of cancer-derived molecules for liquid biopsies. Here, we studied the dynamics of EV levels in the plasma of breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC) and explored the relevance of their RNA cargo for the prediction of patients’ response to the therapy. EVs were isolated from serial blood samples collected at the time of diagnosis, at the end of NAC, and 7 days, 6, and 12 months after the surgery from 32 patients with locally advanced BC, and 30 cancer-free healthy controls (HCs) and quantified by nanoparticle tracking analysis. The pre-treatment levels of EVs in BC patients were higher than in HCs, significantly increased during the NAC and surgery, and decreased to the levels found in HCs 6 months after surgery, thus showing that a substantial fraction of plasma EVs in BC patients are produced due to the disease processes and treatment. RNA sequencing analysis revealed that the changes in the EV levels were associated with the alterations in the proportions of various RNA biotypes in EVs. To search for RNA biomarkers that predict response to the NAC, patients were dichotomized as responders and non-responders based on Miller-Payne grades and differential expression analyses were carried out between responders and non-responders, and HCs. This resulted in the identification of 6 miRNAs, 4 lncRNAs, and 1 snoRNA that had significantly higher levels in EVs from non-responders than responders at the time of diagnosis and throughout the NAC, and significantly lower levels in HCs, thus representing biomarkers for the prediction of response to NAC at the time of diagnosis. In addition, we found 14 RNAs representing piRNA, miRNA, lncRNA, snoRNA, and snRNA biotypes that were induced by NAC in non-responders and 2 snoRNAs and 1 piRNA that were induced by NAC in patients with early disease progression, thus warranting further functional studies on their role in chemoresistance and metastasis. |
| first_indexed | 2024-04-12T11:42:47Z |
| format | Article |
| id | doaj.art-68b46f102af94542a2754e711df68993 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T11:42:47Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-68b46f102af94542a2754e711df689932022-12-22T03:34:32ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.10058121005812Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapyLilite Sadovska0Pawel Zayakin1Kristaps Eglītis2Edgars Endzeliņš3Ilze Radoviča-Spalviņa4Elīza Avotiņa5Jānis Auders6Laura Keiša7Inta Liepniece-Karele8Inta Liepniece-Karele9Mārcis Leja10Jānis Eglītis11Jānis Eglītis12Aija Linē13Cancer Biomarker group, Latvian Biomedical Research and Study Centre, Riga, LatviaCancer Biomarker group, Latvian Biomedical Research and Study Centre, Riga, LatviaLatvian Oncology Center, Riga Eastern Clinical University Hospital, Riga, LatviaCancer Biomarker group, Latvian Biomedical Research and Study Centre, Riga, LatviaGenera Ltd., Riga, LatviaInstitute of Clinical and Preventive Medicine, University of Latvia, Riga, LatviaCancer Biomarker group, Latvian Biomedical Research and Study Centre, Riga, LatviaCancer Biomarker group, Latvian Biomedical Research and Study Centre, Riga, LatviaLatvian Oncology Center, Riga Eastern Clinical University Hospital, Riga, LatviaDepartment of Pathology, Riga Stradins University, Riga, LatviaInstitute of Clinical and Preventive Medicine, University of Latvia, Riga, LatviaLatvian Oncology Center, Riga Eastern Clinical University Hospital, Riga, LatviaUniversity of Latvia, Faculty of Medicine, University of Latvia, Riga, LatviaCancer Biomarker group, Latvian Biomedical Research and Study Centre, Riga, LatviaExtracellular vesicles (EVs) are g7aining increased attention as carriers of cancer-derived molecules for liquid biopsies. Here, we studied the dynamics of EV levels in the plasma of breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC) and explored the relevance of their RNA cargo for the prediction of patients’ response to the therapy. EVs were isolated from serial blood samples collected at the time of diagnosis, at the end of NAC, and 7 days, 6, and 12 months after the surgery from 32 patients with locally advanced BC, and 30 cancer-free healthy controls (HCs) and quantified by nanoparticle tracking analysis. The pre-treatment levels of EVs in BC patients were higher than in HCs, significantly increased during the NAC and surgery, and decreased to the levels found in HCs 6 months after surgery, thus showing that a substantial fraction of plasma EVs in BC patients are produced due to the disease processes and treatment. RNA sequencing analysis revealed that the changes in the EV levels were associated with the alterations in the proportions of various RNA biotypes in EVs. To search for RNA biomarkers that predict response to the NAC, patients were dichotomized as responders and non-responders based on Miller-Payne grades and differential expression analyses were carried out between responders and non-responders, and HCs. This resulted in the identification of 6 miRNAs, 4 lncRNAs, and 1 snoRNA that had significantly higher levels in EVs from non-responders than responders at the time of diagnosis and throughout the NAC, and significantly lower levels in HCs, thus representing biomarkers for the prediction of response to NAC at the time of diagnosis. In addition, we found 14 RNAs representing piRNA, miRNA, lncRNA, snoRNA, and snRNA biotypes that were induced by NAC in non-responders and 2 snoRNAs and 1 piRNA that were induced by NAC in patients with early disease progression, thus warranting further functional studies on their role in chemoresistance and metastasis.https://www.frontiersin.org/articles/10.3389/fonc.2022.1005812/fullextracellular vesiclesRNA biotypessnoRNAbreast cancerneoadjuvant chemotherapyRNA sequencing |
| spellingShingle | Lilite Sadovska Pawel Zayakin Kristaps Eglītis Edgars Endzeliņš Ilze Radoviča-Spalviņa Elīza Avotiņa Jānis Auders Laura Keiša Inta Liepniece-Karele Inta Liepniece-Karele Mārcis Leja Jānis Eglītis Jānis Eglītis Aija Linē Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy Frontiers in Oncology extracellular vesicles RNA biotypes snoRNA breast cancer neoadjuvant chemotherapy RNA sequencing |
| title | Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy |
| title_full | Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy |
| title_fullStr | Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy |
| title_full_unstemmed | Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy |
| title_short | Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy |
| title_sort | comprehensive characterization of rna cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy |
| topic | extracellular vesicles RNA biotypes snoRNA breast cancer neoadjuvant chemotherapy RNA sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1005812/full |
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