Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Medical Clinical Laboratory, Yibin Hospital of T.C.M, Yibin, China.
Aging (Albany NY). 2024 Jan 12;16(1):872-910. doi: 10.18632/aging.205426.
X-ray repair cross-complementation group 1 (XRCC1) is a pivotal contributor to base excision repair, and its dysregulation has been implicated in the oncogenicity of various human malignancies. However, a comprehensive pan-cancer analysis investigating the prognostic value, immunological functions, and epigenetic associations of XRCC1 remains lacking. To address this knowledge gap, we conducted a systematic investigation employing bioinformatics techniques across 33 cancer types. Our analysis encompassed XRCC1 expression levels, prognostic and diagnostic implications, epigenetic profiles, immune and molecular subtypes, Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), immune checkpoints, and immune infiltration, leveraging data from TCGA, GTEx, CELL, Human Protein Atlas, Ualcan, and cBioPortal databases. Notably, XRCC1 displayed both positive and negative correlations with prognosis across different tumors. Epigenetic analysis revealed associations between XRCC1 expression and DNA methylation patterns in 10 cancer types, as well as enhanced phosphorylation. Furthermore, XRCC1 expression demonstrated associations with TMB and MSI in the majority of tumors. Interestingly, XRCC1 gene expression exhibited a negative correlation with immune cell infiltration levels, except for a positive correlation with M1 and M2 macrophages and monocytes in most cancers. Additionally, we observed significant correlations between XRCC1 and immune checkpoint gene expression levels. Lastly, our findings implicated XRCC1 in DNA replication and repair processes, shedding light on the precise mechanisms underlying its oncogenic effects. Overall, our study highlights the potential of XRCC1 as a prognostic and immunological pan-cancer biomarker, thereby offering a novel target for tumor immunotherapy.
X 射线修复交叉互补基因 1(XRCC1)是碱基切除修复的关键贡献者,其失调与各种人类恶性肿瘤的致癌性有关。然而,全面的泛癌分析研究 XRCC1 的预后价值、免疫功能和表观遗传关联仍然缺乏。为了解决这一知识空白,我们使用生物信息学技术对 33 种癌症类型进行了系统调查。我们的分析包括 XRCC1 表达水平、预后和诊断意义、表观遗传谱、免疫和分子亚型、肿瘤突变负担(TMB)、微卫星不稳定性(MSI)、免疫检查点和免疫浸润,利用来自 TCGA、GTEx、CELL、Human Protein Atlas、Ualcan 和 cBioPortal 数据库的数据。值得注意的是,XRCC1 在不同的肿瘤中与预后呈正相关和负相关。表观遗传分析显示,在 10 种癌症中,XRCC1 表达与 DNA 甲基化模式之间存在关联,以及磷酸化增强。此外,在大多数肿瘤中,XRCC1 表达与 TMB 和 MSI 相关。有趣的是,XRCC1 基因表达与免疫细胞浸润水平呈负相关,除了在大多数癌症中与 M1 和 M2 巨噬细胞和单核细胞呈正相关。此外,我们观察到 XRCC1 与免疫检查点基因表达水平之间存在显著相关性。最后,我们的研究结果表明 XRCC1 参与了 DNA 复制和修复过程,揭示了其致癌作用的确切机制。总之,我们的研究强调了 XRCC1 作为一种预后和免疫泛癌生物标志物的潜力,为肿瘤免疫治疗提供了一个新的靶点。