Tian Zuguo, Liu Shuiyu, Weng Chunlan
Department of Hematology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
PeerJ. 2025 Sep 16;13:e20001. doi: 10.7717/peerj.20001. eCollection 2025.
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) subtype in adults. Dysregulation of replication factor C subunit 3 (RFC3) gene expression were associated with disease progression and poor prognosis in various cancer types. However, its significance in DLBCL remains largely unexplored. This study aimed to characterize RFC3 expression patterns, clinical relevance, functional mechanisms, and potential therapeutic implications in DLBCL.
Multi-omics analyses were performed using data extracted from the Gene Expression Omnibus (GEO) project (GSE181063, GSE10846, GSE32918, GSE31312, GSE32018, and GSE12453) and The Cancer Genome Atlas (TCGA). RFC3 expression was validated immunohistochemistry (IHC) in DLBCL samples. Survival analysis was conducted using the Kaplan-Meier method. The chi-square test was used to assess the association between RFC3 expression and clinical characteristics of DLBCL. Gene Set Enrichment Analysis (GSEA) was employed to identify tumor signaling pathways associated with RFC3. Immune infiltration was evaluated using the Immuno-Oncology Biological Research (IOBR) package. Drug sensitivity analysis was performed using the oncoPredict package, and immunotherapy response was assessed via the IMvigor210 dataset. Pan-cancer analysis was conducted using the easyTCGA and TCGAplot packages available on the R software.
RFC3 expression was significantly upregulated in DLBCL. High RFC3 expression was closely associated with poor prognosis, adverse clinical features, and adverse tumor microenvironment characteristics in DLBCL patients. Furthermore, multiple tumor proliferation and cancer-related signaling pathways were significantly enriched in the high RFC3 expression group. The pan-cancer analysis also revealed elevated RFC3 expression across several tumor types. Elevated RFC3 expression was strongly correlated with worse tumor prognosis.
RFC3 may serve as a novel prognostic biomarker and a potential therapeutic target for DLBCL. Further investigations into the mechanisms underlying RFC3 dysregulation may provide important insights for future diagnostic and therapeutic strategies.
弥漫性大B细胞淋巴瘤（DLBCL）是成人中最常见的非霍奇金淋巴瘤（NHL）亚型。复制因子C亚基3（RFC3）基因表达失调与多种癌症类型的疾病进展和不良预后相关。然而，其在DLBCL中的意义仍 largely 未被探索。本研究旨在表征RFC3在DLBCL中的表达模式、临床相关性、功能机制及潜在治疗意义。
使用从基因表达综合数据库（GEO）项目（GSE181063、GSE10846、GSE32918、GSE31312、GSE32018和GSE12453）以及癌症基因组图谱（TCGA）中提取的数据进行多组学分析。通过免疫组织化学（IHC）验证DLBCL样本中RFC3的表达。采用Kaplan-Meier方法进行生存分析。使用卡方检验评估RFC3表达与DLBCL临床特征之间的关联。采用基因集富集分析（GSEA）来识别与RFC3相关的肿瘤信号通路。使用免疫肿瘤生物学研究（IOBR）软件包评估免疫浸润情况。使用oncoPredict软件包进行药物敏感性分析，并通过IMvigor210数据集评估免疫治疗反应。使用R软件上可用的easyTCGA和TCGAplot软件包进行泛癌分析。
DLBCL中RFC3表达显著上调。高RFC3表达与DLBCL患者的不良预后、不良临床特征及不良肿瘤微环境特征密切相关。此外，多个肿瘤增殖和癌症相关信号通路在高RFC3表达组中显著富集。泛癌分析还显示多种肿瘤类型中RFC3表达升高。RFC3表达升高与更差的肿瘤预后密切相关。
RFC3可能作为DLBCL的一种新型预后生物标志物和潜在治疗靶点。对RFC3失调潜在机制的进一步研究可能为未来的诊断和治疗策略提供重要见解。
