PLEKHG7 Expression: A Biomarker for Prognosis and Targeted Therapy in Diffuse Large B-cell Lymphoma.

IF 1.1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Protein and Peptide Letters Pub Date : 2025-10-03 DOI:10.2174/0109298665398122250929045705

Guizhen Lyu, Dongbing Li

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引用次数: 0

Abstract

Introduction: Pleckstrin homology and RhoGEF domain-containing G7 (PLEKHG7) is a largely uncharacterized gene whose role in diffuse large B-cell lymphoma (DLBCL) remains unexplored. Thus, we aimed to profile PLEKHG7 expression, assess its prognostic value, and explore therapeutic implications.

Methods: RNA-seq data from TCGA-DLBCL (n=48) and GTEx normal tissues were analyzed via UCSC XENA. Differential expression was tested using the Wilcoxon rank-sum test and FDR correction. Prognostic significance was evaluated by Kaplan-Meier and multivariate Cox regression (nomogram). Gene set enrichment analysis (GSEA) mapped PLEKHG7-associated pathways. Drug sensitivity correlations were extracted from RNAactDrug. qRT-PCR validated expression in DLBCL cell lines (OCI-Ly3, SU-DHL-4) versus normal B lymphocytes (GM12878).

Results: PLEKHG7 was markedly up-regulated in DLBCL tissues (P < 0.001) and cell lines versus normal controls (AUC = 0.739). High PLEKHG7 expression predicted inferior overall survival (HR = 8.88; 95% CI: 1.09-72.27; P = 0.041) and remained an independent prognostic factor (HR = 10.109; P = 0.033). GSEA linked PLEKHG7 to ribosome, oxidative phosphorylation, proteasome, cytokine-cytokine receptor interaction, spliceosome, and ECM-receptor pathways. Elevated PLEKHG7 negatively correlated with sensitivity to idelalisib, omipalisib, belinostat, methotrexate, and dacinostat.

Discussion: The study's limitations include reliance on bioinformatics data and the lack of functional validation. Further research is needed to elucidate the molecular mechanisms underlying PLEKHG7's role in DLBCL and validate its clinical utility.

Conclusion: PLEKHG7 is significantly overexpressed in DLBCL and independently predicts poor prognosis. Its association with key oncogenic pathways and drug resistance underscores its potential as both a prognostic biomarker and a therapeutic target, warranting further functional validation.

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PLEKHG7表达：弥漫性大b细胞淋巴瘤预后和靶向治疗的生物标志物

Pleckstrin同源性和含RhoGEF结构域的G7 （PLEKHG7）是一个很大程度上未被表征的基因，其在弥漫性大b细胞淋巴瘤（DLBCL）中的作用尚不清楚。因此，我们旨在分析PLEKHG7的表达，评估其预后价值，并探讨其治疗意义。方法：采用UCSC XENA对TCGA-DLBCL （n=48）和GTEx正常组织的RNA-seq数据进行分析。采用Wilcoxon秩和检验和FDR校正对差异表达进行检验。采用Kaplan-Meier和多变量Cox回归（nomogram）评估预后意义。基因集富集分析（GSEA）绘制了plekhg7相关通路。从RNAactDrug中提取药物敏感性相关性。qRT-PCR验证了DLBCL细胞系（OCI-Ly3, SU-DHL-4）与正常B淋巴细胞（GM12878）的表达。结果：与正常对照相比，PLEKHG7在DLBCL组织和细胞系中明显上调（P < 0.001）（AUC = 0.739）。PLEKHG7高表达预示较差的总生存期（HR = 8.88; 95% CI: 1.09-72.27; P = 0.041），并且仍然是一个独立的预后因素（HR = 10.109; P = 0.033）。GSEA将PLEKHG7与核糖体、氧化磷酸化、蛋白酶体、细胞因子-细胞因子受体相互作用、剪接体和ecm受体途径联系起来。PLEKHG7升高与对理想拉利西、奥米帕利西、贝利诺他、甲氨蝶呤和dacinostat的敏感性呈负相关。讨论：该研究的局限性包括依赖于生物信息学数据和缺乏功能验证。需要进一步的研究来阐明PLEKHG7在DLBCL中作用的分子机制并验证其临床应用。结论：PLEKHG7在DLBCL中显著过表达，可独立预测预后不良。它与关键的致癌途径和耐药性的关联强调了它作为预后生物标志物和治疗靶点的潜力，需要进一步的功能验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Protein and Peptide Letters 生物-生化与分子生物学

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

2 months

期刊介绍： Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis