Peripheral myelin protein 2 is underexpressed in early-onset colorectal cancer and inhibits metastasis.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-06-05 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1610003

Zhiyu Yu, Sen Wang, Peng Xu, Cheng Zhang

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引用次数: 0

Abstract

Background: The occurrence and fatality rates of early-onset colorectal cancer (EOCRC) are increasing, with metastasis being one of the primary causes of the high mortality rate in EOCRC patients. Currently, there is a shortage of biomarkers for diagnosis and targets for treatment with optimal efficacy and reliability. This study aims to identify biomarkers associated with metastasis to provide effective diagnostic strategies for EOCRC patients.

Methods: Expression datasets were retrieved from The Cancer Genome Atlas (TCGA) database and analyzed for differentially expressed genes (DEGs). Subsequently, weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules associated with EOCRC metastasis. Feature genes were selected using machine learning and tdiagnostic performance of these genes was assessed with receiver operating characteristic (ROC) curves. We validated peripheral myelin protein 2 (PMP2) expression levels in EOCRC tissues at the molecular and protein levels using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Finally, the invasive and migratory capabilities of PMP2 were assessed in this study using Transwell assays.

Results: The analysis identified 1,411 DEGs in EOCRC and 3,434 DEGs in late-onset colorectal cancer (LOCRC). Subsequently, WGCNA filtered out module genes specifically associated with metastasis in EOCRC, leading to 44 genes. We identified four feature genes by analyzing these genes using machine learning algorithms and taking the intersection: LINC02268, AC092652.1, GRIK1, and PMP2. The ROC curve indicated that these four genes are vitally involved in EOCRC. Further, qRT-PCR and IHC highlighted that PMP2 was downregulated in EOCRC tumor tissues compared to normal tissues. Moreover, Transwell assays revealed that PMP2 inhibited the invasion and migration of EOCRC.

Conclusion: PMP2 has low expression in EOCRC tissues and inhibits EOCRC metastasis, serving as a potential biomarker and therapeutic target for EOCRC treatment.

查看原文本刊更多论文

外周髓鞘蛋白2在早发性结直肠癌中低表达并抑制转移。

背景：早发性结直肠癌（EOCRC）的发病率和病死率不断上升，转移是导致早发性结直肠癌患者高死亡率的主要原因之一。目前，缺乏具有最佳疗效和可靠性的诊断生物标志物和治疗靶点。本研究旨在鉴定与转移相关的生物标志物，为EOCRC患者提供有效的诊断策略。方法：从癌症基因组图谱（TCGA）数据库中检索表达数据集，分析差异表达基因（DEGs）。随后，采用加权基因共表达网络分析（WGCNA）确定与EOCRC转移相关的基因模块。使用机器学习选择特征基因，并使用受试者工作特征（ROC）曲线评估这些基因的诊断性能。我们利用定量逆转录聚合酶链式反应（qRT-PCR）和免疫组织化学（IHC）在分子和蛋白水平上验证了外周血髓鞘蛋白2 （PMP2）在EOCRC组织中的表达水平。最后，本研究使用Transwell法评估了PMP2的侵袭和迁移能力。结果：该分析在EOCRC中鉴定出1,411个DEGs，在晚发性结直肠癌（LOCRC）中鉴定出3,434个DEGs。随后，WGCNA筛选出与EOCRC转移特异性相关的模块基因，共筛选出44个基因。我们通过使用机器学习算法分析这些基因并取交集，确定了四个特征基因：LINC02268， AC092652.1， GRIK1和PMP2。ROC曲线显示这4个基因在EOCRC中起重要作用。此外，qRT-PCR和免疫组化结果显示，与正常组织相比，EOCRC肿瘤组织中PMP2表达下调。此外，Transwell实验显示PMP2抑制了EOCRC的侵袭和迁移。结论：PMP2在EOCRC组织中低表达，可抑制EOCRC转移，是治疗EOCRC的潜在生物标志物和治疗靶点。

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

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.