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Identification of multiomics map and key biomarkers in uveal melanoma with chromosome 3 loss

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机构： [1]Vascular Surgery Department of Affiliated Hospital of North Sichuan Medical College. [2]Hepatobiliary, Pancreatic and Intestinal Research Institute of North Sichuan Medical College. [3]Department of Clinical Medicine, North Sichuan Medical College. [4]Department of Pharmacy, The Second Affiliated Hospital of North Sichuan Medical College. [5]Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, Guangxi, People's Republic of China. [6]Endocrine Department of Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan. [7]Infectious Diseases D of Affiliated Hospital of North Sichuan Medical College.

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关键词： chromosome 3 GRIN2A machine learning multiomics uveal melanoma

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Chromosome 3 loss is an independent risk factor for uveal melanoma (UM), but its exact molecular mechanisms remain unclear. This study was designed to investigate the relationship between chromosome 3 loss and molecular alterations at multiple levels to construct a prognostic model.Forty-four UM cases with chromosome 3 loss (chr3 del group) and 36 UM cases without copy number variation on chromosome 3 (chr3 wt group) were collected from the Cancer Genome Atlas (TCGA). The TCGA dataset was subjected to a univariate Cox regression analysis to identify different expressed genes, and a subsequent random forest algorithm analysis revealed significant changes in different expressed genes, which were used to develop key biomarkers for UM. Following that, the immune cell infiltration analysis and drug sensitivity analyses were carried out. The UM cell line was then utilized to investigate the potential functions of the key biomarker via cell apoptosis, proliferation, cycle assays, WB, and RT-qPCR.By analyzing the 80 cases data in TCGA, the authors unveiled molecular changes relevant to loss of chromosome 3 in UM as well as their poor survival. In addition, machine learning analysis identified three hub genes (GRIN2A, ACAN, and MMP9) as potential therapeutic targets. The differentially enriched pathways between the two groups were mainly about immune-system activity, and hub genes expression was also highly correlated with immune infiltration levels.Chromosome 3 loss has considerable clinical significance for UM, and GRIN2A may be useful in diagnosing, treating, and prognosticating the condition.Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

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第一作者机构： [1]Vascular Surgery Department of Affiliated Hospital of North Sichuan Medical College. [2]Hepatobiliary, Pancreatic and Intestinal Research Institute of North Sichuan Medical College.

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通讯机构： [7]Infectious Diseases D of Affiliated Hospital of North Sichuan Medical College. [*1]Infectious Diseases Department of Affiliated Hospital of North Sichuan Medical College, Sichuan Province, People’s Republic of China

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