Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies
Over the past decade, extracellular vesicles (EVs) have emerged as a promising source of cancer-derived RNAs for liquid biopsies. However, blood contains a pool of heterogeneous EVs released by a variety of cell types, making the identification of cancer RNA biomarkers challenging. Here, we performe...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/17/4329 |
| _version_ | 1797582763854921728 |
|---|---|
| author | Pawel Zayakin Lilite Sadovska Kristaps Eglītis Nadezhda Romanchikova Ilze Radoviča-Spalviņa Edgars Endzeliņš Inta Liepniece-Karele Jānis Eglītis Aija Linē |
| author_facet | Pawel Zayakin Lilite Sadovska Kristaps Eglītis Nadezhda Romanchikova Ilze Radoviča-Spalviņa Edgars Endzeliņš Inta Liepniece-Karele Jānis Eglītis Aija Linē |
| author_sort | Pawel Zayakin |
| collection | DOAJ |
| description | Over the past decade, extracellular vesicles (EVs) have emerged as a promising source of cancer-derived RNAs for liquid biopsies. However, blood contains a pool of heterogeneous EVs released by a variety of cell types, making the identification of cancer RNA biomarkers challenging. Here, we performed deep sequencing of plasma EV RNA cargo in 32 patients with locally advanced breast cancer (BC) at diagnosis and 7 days after breast surgery and in 30 cancer-free healthy controls (HCs). To identify BC-derived RNA biomarkers, we searched for RNAs that had higher levels in BC EVs at the time of diagnosis compared with HCs and decreased after surgery. Data analysis showed that the fractions of miRNAs, snRNAs, snoRNAs, and tRFs were increased, but the fraction of lncRNAs was decreased in BC EVs as compared to HCs. BC-derived biomarker candidates were identified across various RNA biotypes. Considered individually, they had very high specificity but moderate sensitivity for the detection of BC, whereas a biomarker model composed of eight RNAs: SNORD3H, SNORD1C, SNORA74D, miR-224-5p, piR-32949, lnc-IFT-122-2, lnc-C9orf50-4, and lnc-FAM122C-3 was able to distinguish BC from HC EVs with an AUC of 0.902 (95% CI = 0.872–0.931, <i>p</i> = 3.4 × 10<sup>−9</sup>) in leave-one-out cross-validation. Furthermore, a number of RNA biomarkers were correlated with the ER and HER2 expression and additional biomarker models were created to predict hormone receptor and HER2 status. Overall, this study demonstrated that the RNA composition of plasma EVs is altered in BC patients and that they contain cancer-derived RNA biomarkers that can be used for BC detection and monitoring using liquid biopsies. |
| first_indexed | 2024-03-10T23:27:08Z |
| format | Article |
| id | doaj.art-d5ce07b6de5f4a62827eefcda47117de |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T23:27:08Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d5ce07b6de5f4a62827eefcda47117de2023-11-19T07:56:16ZengMDPI AGCancers2072-66942023-08-011517432910.3390/cancers15174329Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid BiopsiesPawel Zayakin0Lilite Sadovska1Kristaps Eglītis2Nadezhda Romanchikova3Ilze Radoviča-Spalviņa4Edgars Endzeliņš5Inta Liepniece-Karele6Jānis Eglītis7Aija Linē8Latvian Biomedical Research and Study Centre, Ratsupites Str. 1, k-1, LV-1067 Riga, LatviaLatvian Biomedical Research and Study Centre, Ratsupites Str. 1, k-1, LV-1067 Riga, LatviaLatvian Oncology Center, Riga Eastern Clinical University Hospital, LV-1038 Riga, LatviaLatvian Biomedical Research and Study Centre, Ratsupites Str. 1, k-1, LV-1067 Riga, LatviaGenera Ltd., Mārupes Str. 22, LV-1002 Riga, LatviaLatvian Biomedical Research and Study Centre, Ratsupites Str. 1, k-1, LV-1067 Riga, LatviaDepartment of Pathology, Riga Stradins University, LV-1007 Riga, LatviaLatvian Oncology Center, Riga Eastern Clinical University Hospital, LV-1038 Riga, LatviaLatvian Biomedical Research and Study Centre, Ratsupites Str. 1, k-1, LV-1067 Riga, LatviaOver the past decade, extracellular vesicles (EVs) have emerged as a promising source of cancer-derived RNAs for liquid biopsies. However, blood contains a pool of heterogeneous EVs released by a variety of cell types, making the identification of cancer RNA biomarkers challenging. Here, we performed deep sequencing of plasma EV RNA cargo in 32 patients with locally advanced breast cancer (BC) at diagnosis and 7 days after breast surgery and in 30 cancer-free healthy controls (HCs). To identify BC-derived RNA biomarkers, we searched for RNAs that had higher levels in BC EVs at the time of diagnosis compared with HCs and decreased after surgery. Data analysis showed that the fractions of miRNAs, snRNAs, snoRNAs, and tRFs were increased, but the fraction of lncRNAs was decreased in BC EVs as compared to HCs. BC-derived biomarker candidates were identified across various RNA biotypes. Considered individually, they had very high specificity but moderate sensitivity for the detection of BC, whereas a biomarker model composed of eight RNAs: SNORD3H, SNORD1C, SNORA74D, miR-224-5p, piR-32949, lnc-IFT-122-2, lnc-C9orf50-4, and lnc-FAM122C-3 was able to distinguish BC from HC EVs with an AUC of 0.902 (95% CI = 0.872–0.931, <i>p</i> = 3.4 × 10<sup>−9</sup>) in leave-one-out cross-validation. Furthermore, a number of RNA biomarkers were correlated with the ER and HER2 expression and additional biomarker models were created to predict hormone receptor and HER2 status. Overall, this study demonstrated that the RNA composition of plasma EVs is altered in BC patients and that they contain cancer-derived RNA biomarkers that can be used for BC detection and monitoring using liquid biopsies.https://www.mdpi.com/2072-6694/15/17/4329extracellular vesiclesbreast cancerRNA sequencingsnoRNAliquid biopsydiagnostic biomarker |
| spellingShingle | Pawel Zayakin Lilite Sadovska Kristaps Eglītis Nadezhda Romanchikova Ilze Radoviča-Spalviņa Edgars Endzeliņš Inta Liepniece-Karele Jānis Eglītis Aija Linē Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies Cancers extracellular vesicles breast cancer RNA sequencing snoRNA liquid biopsy diagnostic biomarker |
| title | Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies |
| title_full | Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies |
| title_fullStr | Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies |
| title_full_unstemmed | Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies |
| title_short | Extracellular Vesicles—A Source of RNA Biomarkers for the Detection of Breast Cancer in Liquid Biopsies |
| title_sort | extracellular vesicles a source of rna biomarkers for the detection of breast cancer in liquid biopsies |
| topic | extracellular vesicles breast cancer RNA sequencing snoRNA liquid biopsy diagnostic biomarker |
| url | https://www.mdpi.com/2072-6694/15/17/4329 |
| work_keys_str_mv | AT pawelzayakin extracellularvesiclesasourceofrnabiomarkersforthedetectionofbreastcancerinliquidbiopsies AT lilitesadovska extracellularvesiclesasourceofrnabiomarkersforthedetectionofbreastcancerinliquidbiopsies AT kristapseglitis extracellularvesiclesasourceofrnabiomarkersforthedetectionofbreastcancerinliquidbiopsies AT nadezhdaromanchikova extracellularvesiclesasourceofrnabiomarkersforthedetectionofbreastcancerinliquidbiopsies AT ilzeradovicaspalvina extracellularvesiclesasourceofrnabiomarkersforthedetectionofbreastcancerinliquidbiopsies AT edgarsendzelins extracellularvesiclesasourceofrnabiomarkersforthedetectionofbreastcancerinliquidbiopsies AT intaliepniecekarele extracellularvesiclesasourceofrnabiomarkersforthedetectionofbreastcancerinliquidbiopsies AT janiseglitis extracellularvesiclesasourceofrnabiomarkersforthedetectionofbreastcancerinliquidbiopsies AT aijaline extracellularvesiclesasourceofrnabiomarkersforthedetectionofbreastcancerinliquidbiopsies |