School of Life Science, Inner Mongolia University, Hohhot, China.
School of Basic medical, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
J Cell Mol Med. 2024 Jun;28(12):e18478. doi: 10.1111/jcmm.18478.
RFC4 is required for DNA polymerase δ and DNA polymerase ε to initiate DNA template expansion. Downregulated RFC4 inhibits tumour proliferation by causing S-phase arrest and inhibiting mitosis, resulting in the reduction of tumour cells. RFC4 has been implicated that it plays an important role in the initiation and progression of cancers, but a comprehensive analysis of the role of RFC4 in cancer has not been performed. We comprehensively analysed the expression, prognosis, methylation level, splicing level, relationship of RFC4 and immune infiltration, and pan-cancer immunotherapy response used various databases (including TCGA, GTEx, UALCAN, Oncosplicing, TIDE, TISCH, HPA and CAMOIP), and experimented its biological function in HCC. Through pan-cancer analysis, we found that RFC4 is significantly upregulated in most tumours. The tumour patients with high expression of RFC4 have poor prognosis. The methylation level and variable splicing level of RFC4 were abnormal in most tumours compared with the adjacent tissues. Furthermore, RFC4 was closely associated with immune cell infiltration in various cancers. RFC4 was significantly co-expressed with immune checkpoints and other immune-related genes. The expression of RFC4 could indicate the immunotherapy efficacy of some tumours. The RFC4 expression was associated with sensitivity to specific small molecule drugs. Cell experiments have shown that downregulated RFC4 can inhibit cell cycle and tumour cell proliferation. We conducted a systematic pan-cancer analysis of RFC4, and the results showed that RFC4 can serve as a biomarker for cancer diagnosis and prognosis. These findings open new perspectives for precision medicine.
RFC4 对于 DNA 聚合酶 δ 和 DNA 聚合酶 ε 启动 DNA 模板扩展是必需的。下调的 RFC4 通过引起 S 期停滞和抑制有丝分裂来抑制肿瘤增殖，导致肿瘤细胞减少。RFC4 已被证明在癌症的发生和发展中起着重要作用，但尚未对 RFC4 在癌症中的作用进行全面分析。我们综合分析了使用各种数据库（包括 TCGA、GTEx、UALCAN、Oncosplicing、TIDE、TISCH、HPA 和 CAMOIP）的 RFC4 的表达、预后、甲基化水平、剪接水平、与免疫浸润的关系以及泛癌免疫治疗反应，并在 HCC 中实验其生物学功能。通过泛癌分析，我们发现 RFC4 在大多数肿瘤中显著上调。RFC4 高表达的肿瘤患者预后不良。与相邻组织相比，大多数肿瘤中 RFC4 的甲基化水平和可变剪接水平异常。此外，RFC4 与各种癌症中的免疫细胞浸润密切相关。RFC4 与免疫检查点和其他免疫相关基因显著共表达。RFC4 的表达可以指示某些肿瘤的免疫治疗疗效。RFC4 的表达与对特定小分子药物的敏感性相关。细胞实验表明，下调 RFC4 可以抑制细胞周期和肿瘤细胞增殖。我们对 RFC4 进行了系统的泛癌分析，结果表明 RFC4 可以作为癌症诊断和预后的生物标志物。这些发现为精准医学开辟了新的视角。
