Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer
Abstract Background Small cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis. Methods To investigate the fe...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Biomarker Research |
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| Online Access: | https://doi.org/10.1186/s40364-023-00517-1 |
| _version_ | 1797557501729701888 |
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| author | Dong Ha Kim Hyojeong Park Yun Jung Choi Kyungtaek Im Chae Won Lee Da-Som Kim Chan-Gi Pack Hyun-Yi Kim Chang-Min Choi Jae Cheol Lee Wonjun Ji Jin Kyung Rho |
| author_facet | Dong Ha Kim Hyojeong Park Yun Jung Choi Kyungtaek Im Chae Won Lee Da-Som Kim Chan-Gi Pack Hyun-Yi Kim Chang-Min Choi Jae Cheol Lee Wonjun Ji Jin Kyung Rho |
| author_sort | Dong Ha Kim |
| collection | DOAJ |
| description | Abstract Background Small cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis. Methods To investigate the feasibility of early diagnosis of SCLC, we examined exosomal microRNAs (miRNAs) present in serum obtained from patients with SCLC. First, exosomes were isolated in serum from patients with SCLC and healthy individuals and were characterized using particle size and protein markers. Additionally, miRNA array was performed to define SCLC-specific exosomal miRNAs. Second, the obtained miRNAs were further validated employing a large cohort. Finally, the ability to diagnose SCLC was estimated by area under the curve (AUC), and intracellular mRNA change patterns were verified through validated miRNAs. Results From the miRNA array results, we selected 51-miRNAs based on p-values and top 10 differentially expressed genes, and 25-miRNAs were validated using quantitative reverse transcription-polymerase chain reaction. The 25-miRNAs were further validated employing a large cohort. Among them, 7-miRNAs showed significant differences. Furthermore, 6-miRNAs (miR-3565, miR-3124-5p, miR-200b-3p, miR-6515, miR-3126-3p and miR-9-5p) were up-regulated and 1-miRNA (miR-92b-5p) was down-regulated. The AUC value of each miRNA sets between 0.64 and 0.76, however the combined application of 3-miRNAs (miR-200b-3p, miR-3124-5p and miR-92b-5p) remarkably improved the diagnostic value (AUC = 0.93). Gene ontology analysis revealed that the 3-miRNA panel is linked to various oncogene pathways and nervous system development. When the 3-miRNAs were introduced to cells, the resulting changes in total mRNA expression strongly indicated the presence of lung diseases, including lung cancer. In addition, the 3-miRNA panel was significantly associated with a poorer prognosis, although individual miRNAs have not been validated as prognostic markers. Conclusion Our study identified SCLC-specific exosomal miRNAs, and the 3-miRNAs panel (miR-200b-3p, miR-3124-5p and miR-92b-5p) may serve as a diagnostic and prognostic marker for SCLC. Graphical abstract |
| first_indexed | 2024-03-10T17:17:48Z |
| format | Article |
| id | doaj.art-004a40481b604424bf05974497000327 |
| institution | Directory Open Access Journal |
| issn | 2050-7771 |
| language | English |
| last_indexed | 2024-03-10T17:17:48Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj.art-004a40481b604424bf059744970003272023-11-20T10:25:06ZengBMCBiomarker Research2050-77712023-09-0111111410.1186/s40364-023-00517-1Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancerDong Ha Kim0Hyojeong Park1Yun Jung Choi2Kyungtaek Im3Chae Won Lee4Da-Som Kim5Chan-Gi Pack6Hyun-Yi Kim7Chang-Min Choi8Jae Cheol Lee9Wonjun Ji10Jin Kyung Rho11Asan Institute for Life SciencesDepartment of Biomedical Sciences, AMISTAsan Institute for Life SciencesAsan Institute for Life SciencesDepartment of Biomedical Sciences, AMISTDepartment of Biomedical Sciences, AMISTDepartment of Convergence Medicine, University of Ulsan College of MedicineNGeneS IncDepartment of Pulmonary Critical and Care Medicine, University of Ulsan College of MedicineDepartment of Oncology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Pulmonary Critical and Care Medicine, University of Ulsan College of MedicineDepartment of Convergence Medicine, University of Ulsan College of MedicineAbstract Background Small cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis. Methods To investigate the feasibility of early diagnosis of SCLC, we examined exosomal microRNAs (miRNAs) present in serum obtained from patients with SCLC. First, exosomes were isolated in serum from patients with SCLC and healthy individuals and were characterized using particle size and protein markers. Additionally, miRNA array was performed to define SCLC-specific exosomal miRNAs. Second, the obtained miRNAs were further validated employing a large cohort. Finally, the ability to diagnose SCLC was estimated by area under the curve (AUC), and intracellular mRNA change patterns were verified through validated miRNAs. Results From the miRNA array results, we selected 51-miRNAs based on p-values and top 10 differentially expressed genes, and 25-miRNAs were validated using quantitative reverse transcription-polymerase chain reaction. The 25-miRNAs were further validated employing a large cohort. Among them, 7-miRNAs showed significant differences. Furthermore, 6-miRNAs (miR-3565, miR-3124-5p, miR-200b-3p, miR-6515, miR-3126-3p and miR-9-5p) were up-regulated and 1-miRNA (miR-92b-5p) was down-regulated. The AUC value of each miRNA sets between 0.64 and 0.76, however the combined application of 3-miRNAs (miR-200b-3p, miR-3124-5p and miR-92b-5p) remarkably improved the diagnostic value (AUC = 0.93). Gene ontology analysis revealed that the 3-miRNA panel is linked to various oncogene pathways and nervous system development. When the 3-miRNAs were introduced to cells, the resulting changes in total mRNA expression strongly indicated the presence of lung diseases, including lung cancer. In addition, the 3-miRNA panel was significantly associated with a poorer prognosis, although individual miRNAs have not been validated as prognostic markers. Conclusion Our study identified SCLC-specific exosomal miRNAs, and the 3-miRNAs panel (miR-200b-3p, miR-3124-5p and miR-92b-5p) may serve as a diagnostic and prognostic marker for SCLC. Graphical abstracthttps://doi.org/10.1186/s40364-023-00517-1ExosomeExosomal miRNADiagnosisPrognosisSCLC |
| spellingShingle | Dong Ha Kim Hyojeong Park Yun Jung Choi Kyungtaek Im Chae Won Lee Da-Som Kim Chan-Gi Pack Hyun-Yi Kim Chang-Min Choi Jae Cheol Lee Wonjun Ji Jin Kyung Rho Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer Biomarker Research Exosome Exosomal miRNA Diagnosis Prognosis SCLC |
| title | Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer |
| title_full | Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer |
| title_fullStr | Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer |
| title_full_unstemmed | Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer |
| title_short | Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer |
| title_sort | identification of exosomal microrna panel as diagnostic and prognostic biomarker for small cell lung cancer |
| topic | Exosome Exosomal miRNA Diagnosis Prognosis SCLC |
| url | https://doi.org/10.1186/s40364-023-00517-1 |
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