PLEK2: a potential biomarker for metastasis and prognostic evaluation in uveal melanoma

BackgroundUveal melanoma (UVM) is an aggressive tumor known for its high metastatic rate, making it necessary to delineate potential molecules that may promote the development of UVM. PLEK2 has been found to promote the progression and metastasis of some tumors, but its role in UVM has not yet been...

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Main Authors: Yichong Liu, Haiyue Wang, Qian Zhang, Xiaodi Gao, Yiqing Ji, Yuanzhang Zhu, Jingjing Zhang, Wenjuan Luo
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2024.1507576/full
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author Yichong Liu
Haiyue Wang
Qian Zhang
Xiaodi Gao
Yiqing Ji
Yuanzhang Zhu
Jingjing Zhang
Wenjuan Luo
author_facet Yichong Liu
Haiyue Wang
Qian Zhang
Xiaodi Gao
Yiqing Ji
Yuanzhang Zhu
Jingjing Zhang
Wenjuan Luo
author_sort Yichong Liu
collection DOAJ
description BackgroundUveal melanoma (UVM) is an aggressive tumor known for its high metastatic rate, making it necessary to delineate potential molecules that may promote the development of UVM. PLEK2 has been found to promote the progression and metastasis of some tumors, but its role in UVM has not yet been reported. Through this study, we hope to explore the effect of PLEK2 on the prognosis of UVM patients and to discover the potential functional role and intrinsic mechanism of PLEK2.MethodsThe GEO datasets GSE211763 and GSE149920 were analyzed using GEO2R to identify differentially expressed genes that may be associated with UVM progression and metastasis. A Protein-Protein Interaction Network (PPI) was constructed to identify key molecules. The correlation between PLEK2 expression and overall survival was evaluated via GEPIA2, and clinical characteristics of UVM patients were compared based on PLEK2 levels. PLEK2 expression in UVM cell lines was assessed using the CCLE database and confirmed by qPCR and western blot. A weighted correlation network analysis (WGCNA) was performed, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, a search for miRNAs potentially regulating PLEK2 expression was performed using TargetScan, miRWalk, and TarBase databases.ResultsComparative analysis of the GEO datasets unveiled 79 commonly up-regulated genes and 238 commonly down-regulated genes. The PPI network identified 9 hub genes, with PLEK2 significantly linked to reduced overall survival. Clinical comparisons indicated significant differences in cancer status (p = 0.013) and tumor diameter (p = 0.039) between high and low PLEK2 expression groups. Elevated PLEK2 mRNA levels were confirmed in UVM cell lines compared to retinal pigment epithelial cells. PLEK2 was enriched in the calcium signaling pathway and associated with the Wnt/Ca2+ signaling pathway. A total of 21 miRNAs potentially regulating PLEK2 were predicted.ConclusionPLEK2 is upregulated in UVM and correlates with poor patient prognosis, likely influencing the calcium signaling pathway. PLEK2 represents a promising prognostic biomarker and therapeutic target for UVM.
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spelling doaj-art-dbdfd8ece9c64241820fc5e952864ffd2025-08-20T02:36:06ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-12-011110.3389/fmed.2024.15075761507576PLEK2: a potential biomarker for metastasis and prognostic evaluation in uveal melanomaYichong Liu0Haiyue Wang1Qian Zhang2Xiaodi Gao3Yiqing Ji4Yuanzhang Zhu5Jingjing Zhang6Wenjuan Luo7Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Clinical Medicine, First College of Clinical Medicine, Binzhou Medical University, Yantai, ChinaDepartment of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaBackgroundUveal melanoma (UVM) is an aggressive tumor known for its high metastatic rate, making it necessary to delineate potential molecules that may promote the development of UVM. PLEK2 has been found to promote the progression and metastasis of some tumors, but its role in UVM has not yet been reported. Through this study, we hope to explore the effect of PLEK2 on the prognosis of UVM patients and to discover the potential functional role and intrinsic mechanism of PLEK2.MethodsThe GEO datasets GSE211763 and GSE149920 were analyzed using GEO2R to identify differentially expressed genes that may be associated with UVM progression and metastasis. A Protein-Protein Interaction Network (PPI) was constructed to identify key molecules. The correlation between PLEK2 expression and overall survival was evaluated via GEPIA2, and clinical characteristics of UVM patients were compared based on PLEK2 levels. PLEK2 expression in UVM cell lines was assessed using the CCLE database and confirmed by qPCR and western blot. A weighted correlation network analysis (WGCNA) was performed, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, a search for miRNAs potentially regulating PLEK2 expression was performed using TargetScan, miRWalk, and TarBase databases.ResultsComparative analysis of the GEO datasets unveiled 79 commonly up-regulated genes and 238 commonly down-regulated genes. The PPI network identified 9 hub genes, with PLEK2 significantly linked to reduced overall survival. Clinical comparisons indicated significant differences in cancer status (p = 0.013) and tumor diameter (p = 0.039) between high and low PLEK2 expression groups. Elevated PLEK2 mRNA levels were confirmed in UVM cell lines compared to retinal pigment epithelial cells. PLEK2 was enriched in the calcium signaling pathway and associated with the Wnt/Ca2+ signaling pathway. A total of 21 miRNAs potentially regulating PLEK2 were predicted.ConclusionPLEK2 is upregulated in UVM and correlates with poor patient prognosis, likely influencing the calcium signaling pathway. PLEK2 represents a promising prognostic biomarker and therapeutic target for UVM.https://www.frontiersin.org/articles/10.3389/fmed.2024.1507576/fulluveal melanomaPLEK2bioinformatics analysisbiomarkerdifferentially expressed genes
spellingShingle Yichong Liu
Haiyue Wang
Qian Zhang
Xiaodi Gao
Yiqing Ji
Yuanzhang Zhu
Jingjing Zhang
Wenjuan Luo
PLEK2: a potential biomarker for metastasis and prognostic evaluation in uveal melanoma
Frontiers in Medicine
uveal melanoma
PLEK2
bioinformatics analysis
biomarker
differentially expressed genes
title PLEK2: a potential biomarker for metastasis and prognostic evaluation in uveal melanoma
title_full PLEK2: a potential biomarker for metastasis and prognostic evaluation in uveal melanoma
title_fullStr PLEK2: a potential biomarker for metastasis and prognostic evaluation in uveal melanoma
title_full_unstemmed PLEK2: a potential biomarker for metastasis and prognostic evaluation in uveal melanoma
title_short PLEK2: a potential biomarker for metastasis and prognostic evaluation in uveal melanoma
title_sort plek2 a potential biomarker for metastasis and prognostic evaluation in uveal melanoma
topic uveal melanoma
PLEK2
bioinformatics analysis
biomarker
differentially expressed genes
url https://www.frontiersin.org/articles/10.3389/fmed.2024.1507576/full
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