Pan-Cancer Analysis Reveals PRIM2 as a Potential Biomarker for Diagnosis, Prognosis, and Immunomodulatory

Xi Zhang, Yuanyu Zhang, Leheng Liu, Zheng Gong, Kecheng Zhou
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Abstract

Purpose: DNA primase subunit 2 (PRIM2) is a component of the DNA polymerase α-primase complex involved in DNA replication. Previous studies have implicated PRIM2 in cancer progression, but a comprehensive pan-cancer analysis is lacking. Here, we systematically analyzed PRIM2 across various cancer types to elucidate its potential role in cancer biology.

Methods: The expression data of PRIM2 was obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) databases. A range of bioinformatics tools were employed to analyze the expression of PRIM2 with the correlation of clinical data, diagnosis, prognosis, subtypes, immunomodulatory, and drug sensitivity. Further validation experiments were performed in HT-29 and HepG2 cell lines.

Results: PRIM2 expression was elevated in most tumor tissues, indicating its potential diagnostic value. Elevated PRIM2 levels affected prognosis and survival and varied with clinical status. Mutations and methylation events drove the aberrant expression of PRIM2 in various cancers. Furthermore, PRIM2 was linked to key immunoregulatory genes such as PD-L1 and infiltration of Th2 cells in tumor tissues. Our findings suggested that PRIM2 is correlated to immunotherapy and may be sensitive to specific small molecule PLK1 inhibitors. Knocking down PRIM2 in HT-29 and HepG2 cell lines reduced their proliferation, migration, invasion, and epithelial-mesenchymal transition.

Conclusion: This research highlights the potential of PRIM2 as a biomarker for cancer diagnosis and prognosis, and as a target for immunomodulatory therapy, offering valuable insights for clinical applications.

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泛癌症分析发现 PRIM2 是一种潜在的诊断、预后和免疫调节生物标记物
目的:DNA primase subunit 2(PRIM2)是 DNA 聚合酶α-primase 复合物的一个组成部分,参与 DNA 复制。以前的研究表明 PRIM2 与癌症进展有关联,但缺乏全面的泛癌症分析。在此,我们系统分析了各种癌症类型中的 PRIM2,以阐明其在癌症生物学中的潜在作用:PRIM2的表达数据来自癌症基因组图谱(TCGA)和基因型-组织表达项目(GTEx)数据库。采用一系列生物信息学工具分析了PRIM2的表达与临床数据、诊断、预后、亚型、免疫调节和药物敏感性的相关性。在 HT-29 和 HepG2 细胞系中进行了进一步的验证实验:结果:PRIM2在大多数肿瘤组织中表达升高,表明其具有潜在的诊断价值。PRIM2 水平升高会影响预后和生存,并随临床状况而变化。突变和甲基化事件驱动了 PRIM2 在各种癌症中的异常表达。此外,PRIM2 还与肿瘤组织中的 PD-L1 和 Th2 细胞浸润等关键免疫调节基因有关。我们的研究结果表明,PRIM2与免疫疗法相关,可能对特定的小分子PLK1抑制剂敏感。在HT-29和HepG2细胞系中敲除PRIM2可减少它们的增殖、迁移、侵袭和上皮-间质转化:这项研究强调了 PRIM2 作为癌症诊断和预后生物标记物以及免疫调节疗法靶点的潜力,为临床应用提供了宝贵的见解。
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来源期刊
Comparative and Functional Genomics
Comparative and Functional Genomics 生物-生化与分子生物学
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