Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment
Le Zhuang,1– 6,* Jie Tian,1– 4,7,* Binbin Lai,1– 4,7 Guohong Zhang,1– 4 Hang Li1– 4 1Department of Dermatology, Peking University First Hospital, Beijing, People’s Republic of China; 2National Clinical Research Center for Skin and Immune Diseases, Peking University First Hospital, Be...
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| Format: | Article |
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Dove Medical Press
2023-04-01
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| Series: | Clinical, Cosmetic and Investigational Dermatology |
| Subjects: | |
| Online Access: | https://www.dovepress.com/single-cell-rna-sequencing-reveals-cellular-heterogeneity-in-an-acral--peer-reviewed-fulltext-article-CCID |
| _version_ | 1797847400460582912 |
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| author | Zhuang L Tian J Lai B Zhang G Li H |
| author_facet | Zhuang L Tian J Lai B Zhang G Li H |
| author_sort | Zhuang L |
| collection | DOAJ |
| description | Le Zhuang,1– 6,* Jie Tian,1– 4,7,* Binbin Lai,1– 4,7 Guohong Zhang,1– 4 Hang Li1– 4 1Department of Dermatology, Peking University First Hospital, Beijing, People’s Republic of China; 2National Clinical Research Center for Skin and Immune Diseases, Peking University First Hospital, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Peking University First Hospital, Beijing, People’s Republic of China; 4NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Peking University First Hospital, Beijing, People’s Republic of China; 5Dermatology Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 6Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China; 7Institute of Medical Technology, Peking University Health Science Center, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hang Li, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China, Tel +8613693058190, Fax +861083572350, Email drlihang@126.comBackground: Anti-programmed cell death ligand-1 (anti-PD-L1) immunotherapy is often used for advanced urothelial carcinoma and melanoma, including amelanotic melanoma, a relatively rare subtype with little to no pigment in the tumor cells. However, cellular heterogeneity of amelanotic melanoma during or after anti-PD-L1 immunotherapy treatments has not been described.Purpose: To investigate cellular heterogeneity in acral amelanotic melanoma after immunotherapy exposure.Methods: We evaluated subtle visual changes of the melanoma by dermoscopy and performed a pathological examination to analyze the heterogeneity of microscopic morphological and immunohistochemistry changes. The cellular transcriptional heterogeneity and corresponding biological function profiles of the melanoma were determined by single-cell RNA sequencing (scRNA-seq).Results: The dermoscopic examination revealed black globules and scar-like depigmentation areas against a homogeneous red background. Pigmented and amelanotic melanoma cells were observed microscopically. The pigmented cells were large and contained melanin granules expressing Melan-A and HMB45; the amelanotic cells were small and did not express HMB45. Ki-67 immunohistochemical staining revealed that the pigmented melanoma cells had a higher proliferative ability than the amelanotic cells. scRNA-seq identified three cell clusters: amelanotic cell cluster 1, amelanotic cell cluster 2, and pigmented cell cluster. Furthermore, a pseudo-time trajectory analysis showed that amelanotic cell cluster 2 originated from amelanotic cell cluster 1 and transformed into the pigmented melanoma cell cluster. The expression pattern of melanin synthesis-related and lysosome-endosome-related genes in different cell clusters supported the cell cluster transformation results. Also, upregulated expression of cell cycle genes indicated that the pigmented melanoma cells had a high proliferative ability.Conclusion: Coexisting amelanotic and pigmented melanoma cells indicated cellular heterogeneity in an acral amelanotic melanoma from a patient who underwent immunotherapy treatment. Additionally, the pigmented melanoma cells acquired a higher proliferative ability than the amelanotic melanoma cells.Keywords: amelanotic, acral melanoma, cellular heterogeneity, immunotherapy, drug resistance |
| first_indexed | 2024-04-09T18:11:55Z |
| format | Article |
| id | doaj.art-fc7b5061349a40ed84847127fadcfa33 |
| institution | Directory Open Access Journal |
| issn | 1178-7015 |
| language | English |
| last_indexed | 2024-04-09T18:11:55Z |
| publishDate | 2023-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical, Cosmetic and Investigational Dermatology |
| spelling | doaj.art-fc7b5061349a40ed84847127fadcfa332023-04-13T19:17:09ZengDove Medical PressClinical, Cosmetic and Investigational Dermatology1178-70152023-04-01Volume 161009101882999Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy TreatmentZhuang LTian JLai BZhang GLi HLe Zhuang,1– 6,* Jie Tian,1– 4,7,* Binbin Lai,1– 4,7 Guohong Zhang,1– 4 Hang Li1– 4 1Department of Dermatology, Peking University First Hospital, Beijing, People’s Republic of China; 2National Clinical Research Center for Skin and Immune Diseases, Peking University First Hospital, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Peking University First Hospital, Beijing, People’s Republic of China; 4NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Peking University First Hospital, Beijing, People’s Republic of China; 5Dermatology Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 6Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China; 7Institute of Medical Technology, Peking University Health Science Center, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hang Li, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China, Tel +8613693058190, Fax +861083572350, Email drlihang@126.comBackground: Anti-programmed cell death ligand-1 (anti-PD-L1) immunotherapy is often used for advanced urothelial carcinoma and melanoma, including amelanotic melanoma, a relatively rare subtype with little to no pigment in the tumor cells. However, cellular heterogeneity of amelanotic melanoma during or after anti-PD-L1 immunotherapy treatments has not been described.Purpose: To investigate cellular heterogeneity in acral amelanotic melanoma after immunotherapy exposure.Methods: We evaluated subtle visual changes of the melanoma by dermoscopy and performed a pathological examination to analyze the heterogeneity of microscopic morphological and immunohistochemistry changes. The cellular transcriptional heterogeneity and corresponding biological function profiles of the melanoma were determined by single-cell RNA sequencing (scRNA-seq).Results: The dermoscopic examination revealed black globules and scar-like depigmentation areas against a homogeneous red background. Pigmented and amelanotic melanoma cells were observed microscopically. The pigmented cells were large and contained melanin granules expressing Melan-A and HMB45; the amelanotic cells were small and did not express HMB45. Ki-67 immunohistochemical staining revealed that the pigmented melanoma cells had a higher proliferative ability than the amelanotic cells. scRNA-seq identified three cell clusters: amelanotic cell cluster 1, amelanotic cell cluster 2, and pigmented cell cluster. Furthermore, a pseudo-time trajectory analysis showed that amelanotic cell cluster 2 originated from amelanotic cell cluster 1 and transformed into the pigmented melanoma cell cluster. The expression pattern of melanin synthesis-related and lysosome-endosome-related genes in different cell clusters supported the cell cluster transformation results. Also, upregulated expression of cell cycle genes indicated that the pigmented melanoma cells had a high proliferative ability.Conclusion: Coexisting amelanotic and pigmented melanoma cells indicated cellular heterogeneity in an acral amelanotic melanoma from a patient who underwent immunotherapy treatment. Additionally, the pigmented melanoma cells acquired a higher proliferative ability than the amelanotic melanoma cells.Keywords: amelanotic, acral melanoma, cellular heterogeneity, immunotherapy, drug resistancehttps://www.dovepress.com/single-cell-rna-sequencing-reveals-cellular-heterogeneity-in-an-acral--peer-reviewed-fulltext-article-CCIDamelanoticacral melanomacellular heterogeneityimmunotherapydrug resistance |
| spellingShingle | Zhuang L Tian J Lai B Zhang G Li H Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment Clinical, Cosmetic and Investigational Dermatology amelanotic acral melanoma cellular heterogeneity immunotherapy drug resistance |
| title | Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment |
| title_full | Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment |
| title_fullStr | Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment |
| title_full_unstemmed | Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment |
| title_short | Single-Cell RNA Sequencing Reveals Cellular Heterogeneity in an Acral Amelanotic Melanoma After Immunotherapy Treatment |
| title_sort | single cell rna sequencing reveals cellular heterogeneity in an acral amelanotic melanoma after immunotherapy treatment |
| topic | amelanotic acral melanoma cellular heterogeneity immunotherapy drug resistance |
| url | https://www.dovepress.com/single-cell-rna-sequencing-reveals-cellular-heterogeneity-in-an-acral--peer-reviewed-fulltext-article-CCID |
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