SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma

Abstract Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinf...

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Main Authors: Zhongyi Fan, Jingjing Duan, Pu Luo, Ling Shao, Qiong Chen, Xiaohua Tan, Lei Zhang, Xiaojie Xu
Format: Article
Language:English
Published: Nature Publishing Group 2022-04-01
Series:Cell Death and Disease
Online Access:https://doi.org/10.1038/s41419-022-04718-8
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author Zhongyi Fan
Jingjing Duan
Pu Luo
Ling Shao
Qiong Chen
Xiaohua Tan
Lei Zhang
Xiaojie Xu
author_facet Zhongyi Fan
Jingjing Duan
Pu Luo
Ling Shao
Qiong Chen
Xiaohua Tan
Lei Zhang
Xiaojie Xu
author_sort Zhongyi Fan
collection DOAJ
description Abstract Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and GSE22138 cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.
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spelling doaj.art-e97f96fa79ca4b41a5e6bf4760a364172022-12-22T00:10:36ZengNature Publishing GroupCell Death and Disease2041-48892022-04-0113411110.1038/s41419-022-04718-8SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanomaZhongyi Fan0Jingjing Duan1Pu Luo2Ling Shao3Qiong Chen4Xiaohua Tan5Lei Zhang6Xiaojie Xu7Department of Oncology and Bio-therapeutic Center, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Research Center for Communicable Disease Diagnosis and TreatmentDepartment of Gastrointestinal Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Oncology and Bio-therapeutic Center, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Research Center for Communicable Disease Diagnosis and TreatmentDepartment of Oncology and Bio-therapeutic Center, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Research Center for Communicable Disease Diagnosis and TreatmentDepartment of Oncology and Bio-therapeutic Center, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Research Center for Communicable Disease Diagnosis and TreatmentDepartment of Oncology and Bio-therapeutic Center, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Research Center for Communicable Disease Diagnosis and TreatmentDepartment of Ophthalmology, Xuanwu Hospital Attached to the Capital Medical UniversityDepartment of Genetic Engineering, Beijing Institute of BiotechnologyAbstract Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and GSE22138 cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.https://doi.org/10.1038/s41419-022-04718-8
spellingShingle Zhongyi Fan
Jingjing Duan
Pu Luo
Ling Shao
Qiong Chen
Xiaohua Tan
Lei Zhang
Xiaojie Xu
SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma
Cell Death and Disease
title SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma
title_full SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma
title_fullStr SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma
title_full_unstemmed SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma
title_short SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma
title_sort slc25a38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma
url https://doi.org/10.1038/s41419-022-04718-8
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