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

Fan, Zhongyi1,2,3; Duan, Jingjing4; Luo, Pu; Shao, Ling1,2; Chen, Qiong1,2; Tan, Xiaohua1,2; Zhang, Lei5; Xu, Xiaojie6

2022-04-11

10.1038/s41419-022-04718-8

Cell Death & Disease   影响因子和分区

2041-4889

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.

SCI

英语

第一 ; 通讯

National Natural Science Foundation of China[81972734,82103677]

Cell Biology

Cell Biology

WOS:000784442500002

SPRINGERNATURE

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Res Ctr Communicable Dis Diag & Treatmen, Dept Oncol, Shenzhen 518112, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Res Ctr Communicable Dis Diag & Treatmen, Biotherapeut Ctr, Shenzhen Peoples Hosp 3,Hosp 2, Shenzhen 518112, Peoples R China
3.Gen Hosp PLA, Med Ctr 1, Dept Oncol, Beijing 100853, Peoples R China
4.Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc,Dept Gastrointestinal Onco, Tianjin Key Lab Canc Prevent & Therapy,Tianjins C, Tianjin 300060, Peoples R China
5.Capital Med Univ, Xuanwu Hosp, Dept Ophthalmol, Beijing 100053, Peoples R China
6.Beijing Inst Biotechnol, Dept Genet Engn, Beijing 100850, Peoples R China

Fan, Zhongyi,Duan, Jingjing,Luo, Pu,et al. SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma[J]. Cell Death & Disease,2022,13(4).

Fan, Zhongyi.,Duan, Jingjing.,Luo, Pu.,Shao, Ling.,Chen, Qiong.,...&Xu, Xiaojie.(2022).SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma.Cell Death & Disease,13(4).

Fan, Zhongyi,et al."SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma".Cell Death & Disease 13.4(2022).