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Integrated single-cell and transcriptome sequencing analyses develops a metastasis-based risk score system for prognosis and immunotherapy response in uveal melanoma.
Meng, Shuting; Zhu, Tianye; Fan, Zhiwei; Cheng, Yulan; Dong, Yefeng; Wang, Fengxu; Wang, Xuehai; Dong, Deping; Yuan, Songtao; Zhao, Xinyuan.
Afiliação
  • Meng S; Hai an People's Hospital, Nantong, China.
  • Zhu T; Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • Fan Z; School of Medicine, Nantong University, Nantong, China.
  • Cheng Y; Nantong Key Laboratory of Environmental Toxicology, Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, China.
  • Dong Y; Hai an People's Hospital, Nantong, China.
  • Wang F; Nantong Key Laboratory of Environmental Toxicology, Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, China.
  • Wang X; Nantong Key Laboratory of Environmental Toxicology, Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, China.
  • Dong D; Hai an People's Hospital, Nantong, China.
  • Yuan S; Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • Zhao X; Nantong Key Laboratory of Environmental Toxicology, Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, China.
Front Pharmacol ; 14: 1138452, 2023.
Article em En | MEDLINE | ID: mdl-36843929
ABSTRACT

Background:

Uveal melanoma (UM) is the most frequent ocular neoplasm with a strong metastatic ability. The prognostic value of metastasis-associated genes (MAGs) of UM remains unclear. It is urgent to develop a prognostic score system according to the MAGs of UM.

Methods:

Unsupervised clustering was used to identify MAGs-based molecular subtypes. Cox methods were utilized to generate a prognostic score system. The prognostic ability of the score system was detected by plotting ROC and survival curves. The immune activity and underlying function were depicted by CIBERSORT GSEA algorithms.

Results:

Gene cluster analysis determined two MAGs-based subclusters in UM, which were remarkably different in clinical outcomes. A risk score system containing six MAGs (COL11A1, AREG, TIMP3, ADAM12, PRRX1 and GAS1) was set up. We employed ssGSEA to compare immune activity and immunocyte infiltration between the two risk groups. Notch, JAK/STAT and mTOR pathways were greatly enriched in the high-risk group. Furthermore, we observed that knockdown of AREG could inhibit UM proliferation and metastasis by in vitro assays.

Conclusion:

The MAGs-based subtype and score system in UM can enhance prognosis assessment, and the core system provides valuable reference for clinical decision-making.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Idioma: En Ano de publicação: 2023 Tipo de documento: Article