Integrated analysis reveals the dysfunction of signaling pathways in uveal melanoma
Abstract Background Uveal melanoma (UM) is the most common primary intraocular malignancy with a strong tendency to metastasize. The prognosis is poor once metastasis occurs. The treatment remains challenging for metastatic UM, even though our understanding of UM has advanced, mostly because the com...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-09822-8 |
| _version_ | 1811218956079333376 |
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| author | Songlin Sun Boxia Guo Liang Xu Rui Shi |
| author_facet | Songlin Sun Boxia Guo Liang Xu Rui Shi |
| author_sort | Songlin Sun |
| collection | DOAJ |
| description | Abstract Background Uveal melanoma (UM) is the most common primary intraocular malignancy with a strong tendency to metastasize. The prognosis is poor once metastasis occurs. The treatment remains challenging for metastatic UM, even though our understanding of UM has advanced, mostly because the complexity of the genetic and immunologic background has not been fully explored. Methods Single-cell sequencing data were acquired from a healthy dataset and three UM datasets. The differentially expressed genes between primary and metastatic UM in The Cancer Genome Atlas (TCGA) data were attributed to specific cell types and explained with functional annotation. The analysis for cell–cell communication was conducted by “CellChat” to understand the cell crosstalk among the cell clusters and to delineate the dysfunctional signaling pathways in metastatic UM. CCK-8, EdU and transwell assays were performed to verify the function of the genes of interest. Results We revealed aberrant signaling pathways with distinct functional statuses between primary and metastatic UM by integrating multiple datasets. The crucial signals contributing most to outgoing or incoming signaling of metastasis were identified to uncover the potential targeting genes. The association of these genes with disease risk was estimated based on survival data from TCGA. The key genes associated with proliferation and metastasis were verified. Conclusions Conclusively, we discovered the potential key signals for occurrence and metastasis of UM and provided a theoretical basis for potential clinical application. |
| first_indexed | 2024-04-12T07:16:34Z |
| format | Article |
| id | doaj.art-e95de0361a8b44168c2578eab9792e30 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T07:16:34Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-e95de0361a8b44168c2578eab9792e302022-12-22T03:42:26ZengBMCBMC Cancer1471-24072022-07-0122111310.1186/s12885-022-09822-8Integrated analysis reveals the dysfunction of signaling pathways in uveal melanomaSonglin Sun0Boxia Guo1Liang Xu2Rui Shi3Department of Ophthalmology, Yuncheng Central Hospital, Shanxi Medical UniversityDepartment of Cardiology, Yuncheng Central Hospital, Shanxi Medical UniversityResearch Center for Translational Medicine, East Hospital, Tongji University School of MedicineDepartment of Obstetrics and Gynecology, East Hospital, Tongji University School of MedicineAbstract Background Uveal melanoma (UM) is the most common primary intraocular malignancy with a strong tendency to metastasize. The prognosis is poor once metastasis occurs. The treatment remains challenging for metastatic UM, even though our understanding of UM has advanced, mostly because the complexity of the genetic and immunologic background has not been fully explored. Methods Single-cell sequencing data were acquired from a healthy dataset and three UM datasets. The differentially expressed genes between primary and metastatic UM in The Cancer Genome Atlas (TCGA) data were attributed to specific cell types and explained with functional annotation. The analysis for cell–cell communication was conducted by “CellChat” to understand the cell crosstalk among the cell clusters and to delineate the dysfunctional signaling pathways in metastatic UM. CCK-8, EdU and transwell assays were performed to verify the function of the genes of interest. Results We revealed aberrant signaling pathways with distinct functional statuses between primary and metastatic UM by integrating multiple datasets. The crucial signals contributing most to outgoing or incoming signaling of metastasis were identified to uncover the potential targeting genes. The association of these genes with disease risk was estimated based on survival data from TCGA. The key genes associated with proliferation and metastasis were verified. Conclusions Conclusively, we discovered the potential key signals for occurrence and metastasis of UM and provided a theoretical basis for potential clinical application.https://doi.org/10.1186/s12885-022-09822-8Uveal melanomaSingle-cell RNA sequencingMolecular mechanismHeterogeneityPrognosis |
| spellingShingle | Songlin Sun Boxia Guo Liang Xu Rui Shi Integrated analysis reveals the dysfunction of signaling pathways in uveal melanoma BMC Cancer Uveal melanoma Single-cell RNA sequencing Molecular mechanism Heterogeneity Prognosis |
| title | Integrated analysis reveals the dysfunction of signaling pathways in uveal melanoma |
| title_full | Integrated analysis reveals the dysfunction of signaling pathways in uveal melanoma |
| title_fullStr | Integrated analysis reveals the dysfunction of signaling pathways in uveal melanoma |
| title_full_unstemmed | Integrated analysis reveals the dysfunction of signaling pathways in uveal melanoma |
| title_short | Integrated analysis reveals the dysfunction of signaling pathways in uveal melanoma |
| title_sort | integrated analysis reveals the dysfunction of signaling pathways in uveal melanoma |
| topic | Uveal melanoma Single-cell RNA sequencing Molecular mechanism Heterogeneity Prognosis |
| url | https://doi.org/10.1186/s12885-022-09822-8 |
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