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PIMREG在黑色素瘤中的致癌作用及预后意义

Oncogenic role and prognostic significance of PIMREG in melanoma.

作者信息

Wei Xiao, Jiang Yujia, Xia Tianxiang, Du Jun

机构信息

The First Clinical Medical College, Nanjing Medical University, Nanjing, China.

Stomatological College, Nanjing Medical University, Nanjing, China.

出版信息

Transl Cancer Res. 2025 Feb 28;14(2):1070-1084. doi: 10.21037/tcr-24-1861. Epub 2025 Feb 26.

DOI:10.21037/tcr-24-1861
PMID:40104736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11912051/
Abstract

BACKGROUND

Phosphatidylinositol binding clathrin assembly protein interacting mitotic regulator (PIMREG) plays a significant role in metaphase-to-anaphase transition in cell cycle. Its aberrant expression has been reported to be in correlation with the development of several tumors. However, its role in melanoma remains unknown. This study aimed to investigate the diagnostic and prognostic roles of PIMREG in skin cutaneous melanoma (SKCM).

METHODS

The expression levels of PIMREG were analyzed in SKCM using datasets downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO). The diagnostic accuracy was assessed using the receiver operating characteristic (ROC) curve. PIMREG was correlated to the functional states of SKCM cells using CancerSEA. Additionally, a protein-protein interaction network was constructed using STRING (https://cn.string-db.org), and hub genes were identified using Cytoscape. Enrichment analysis through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) was utilized to explore the potential functions of PIMREG. The single-sample GSEA (ssGSEA) method was employed to investigate the correlation between PIMREG expression and the level of immune infiltration in SKCM. Drug sensitivity and resistance were analyzed using GSCALite and Cellminer.

RESULTS

The expression of PIMREG was significantly higher in SKCM tissues. Its overexpression correlated with poor survival outcome in melanoma patients. ROC analysis also revealed that PIMREG had high diagnostic potential, with area under the ROC curve (AUC) value of 0.874. Multivariate regression also identified PIMREG could serve as an independent diagnostic indicator for SKCM. Using the web tool of CancerSEA, we demonstrated that PIMREG is involved in cell cycle, DNA repair, DNA damage, epithelial-mesenchymal transition (EMT), invasion, and proliferation. Functional enrichment analysis revealed that PIMREG might be correlated with some biological processes (BPs) and important pathways related to cancer, including Wnt signaling and epidermis development.

CONCLUSIONS

PIMREG is a promising diagnostic and prognostic biomarker and may be regarded as a possible therapeutic target for SKCM.

摘要

背景

磷脂酰肌醇结合网格蛋白组装蛋白相互作用有丝分裂调节因子(PIMREG)在细胞周期的中期到后期转换中起重要作用。据报道,其异常表达与多种肿瘤的发生发展相关。然而,其在黑色素瘤中的作用尚不清楚。本研究旨在探讨PIMREG在皮肤黑色素瘤(SKCM)中的诊断和预后作用。

方法

利用从癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)和基因表达综合数据库(GEO)下载的数据集,分析SKCM中PIMREG的表达水平。使用受试者工作特征(ROC)曲线评估诊断准确性。利用CancerSEA将PIMREG与SKCM细胞的功能状态相关联。此外,使用STRING(https://cn.string-db.org)构建蛋白质-蛋白质相互作用网络,并使用Cytoscape识别枢纽基因。通过基因本体论(GO)、京都基因与基因组百科全书(KEGG)和基因集富集分析(GSEA)进行富集分析,以探索PIMREG的潜在功能。采用单样本GSEA(ssGSEA)方法研究PIMREG表达与SKCM中免疫浸润水平的相关性。使用GSCALite和Cellminer分析药物敏感性和耐药性。

结果

PIMREG在SKCM组织中的表达显著更高。其过表达与黑色素瘤患者的不良生存结果相关。ROC分析还显示,PIMREG具有较高的诊断潜力,ROC曲线下面积(AUC)值为0.874。多变量回归还确定PIMREG可作为SKCM的独立诊断指标。使用CancerSEA网络工具,我们证明PIMREG参与细胞周期、DNA修复、DNA损伤、上皮-间质转化(EMT)、侵袭和增殖。功能富集分析表明,PIMREG可能与一些生物学过程(BP)和与癌症相关的重要途径相关,包括Wnt信号通路和表皮发育。

结论

PIMREG是一种有前景的诊断和预后生物标志物,可能被视为SKCM的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/b5d26077f468/tcr-14-02-1070-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/37ec6dabdb7f/tcr-14-02-1070-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/369a20debce9/tcr-14-02-1070-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/f99b018e6b5a/tcr-14-02-1070-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/e4dfe4ff07ca/tcr-14-02-1070-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/b5d26077f468/tcr-14-02-1070-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/37ec6dabdb7f/tcr-14-02-1070-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/47dc583d0416/tcr-14-02-1070-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/5a15a112ec07/tcr-14-02-1070-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/208f9bf7e046/tcr-14-02-1070-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/3e5fb823da06/tcr-14-02-1070-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/369a20debce9/tcr-14-02-1070-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/f99b018e6b5a/tcr-14-02-1070-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9570/11912051/e4dfe4ff07ca/tcr-14-02-1070-f8.jpg
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