Peng Jian, Quan Jichuan, Wang Xiaoru
Anhui Institute of Pediatric Research, Anhui Provincial Children's Hospital, Hefei, Anhui, China.
Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
PLoS Comput Biol. 2025 Aug 25;21(8):e1013374. doi: 10.1371/journal.pcbi.1013374. eCollection 2025 Aug.
While the RNA-binding protein HuR is implicated in individual cancers, its comprehensive diagnostic, prognostic, and immunological roles across diverse cancer types remain unexplored.
We performed an integrated pan-cancer analysis of HuR using public datasets. This encompassed expression profiling, survival analysis, diagnostic accuracy assessment, immune microenvironment characterization, and drug sensitivity prediction. We investigated HuR's regulatory mechanisms through pathway correlation and differential gene expression analyses.
HuR expression was consistently elevated across multiple cancers and correlated with poor patient prognosis. It demonstrated high diagnostic accuracy (>85%) via TMB/PD-L1 biomarkers. High HuR expression was associated with an immunosuppressive tumor microenvironment and reduced efficacy of immune checkpoint inhibitors, establishing it as a key immunoregulatory biomarker. HuR also predicted sensitivity to cell cycle inhibitors and other pathway-targeted drugs. Mechanistically, HuR drives malignancy by dysregulating core processes: cell cycle progression, immune evasion, and cellular metabolism.
Our pan-cancer analysis establishes HuR as a consistently upregulated oncogenic driver across malignancies, functioning as a potential universal biomarker for prognosis and diagnosis. Its critical roles in modulating the immune response and predicting therapeutic sensitivity highlight its importance for personalized cancer treatment strategies. HuR orchestrates tumorigenesis and malignant progression by integrally regulating vital cellular processes.
虽然RNA结合蛋白HuR与个别癌症有关，但其在多种癌症类型中的综合诊断、预后和免疫作用仍未得到探索。
我们使用公共数据集对HuR进行了综合泛癌分析。这包括表达谱分析、生存分析、诊断准确性评估、免疫微环境特征分析和药物敏感性预测。我们通过通路相关性和差异基因表达分析研究了HuR的调控机制。
HuR在多种癌症中表达持续升高，且与患者预后不良相关。通过肿瘤突变负荷（TMB）/程序性死亡受体配体1（PD-L1）生物标志物，它显示出较高的诊断准确性（>85%）。高HuR表达与免疫抑制性肿瘤微环境相关，且免疫检查点抑制剂的疗效降低，这使其成为关键的免疫调节生物标志物。HuR还预测了对细胞周期抑制剂和其他通路靶向药物的敏感性。从机制上讲，HuR通过失调核心过程（细胞周期进程、免疫逃逸和细胞代谢）来驱动恶性肿瘤。
我们的泛癌分析确定HuR是一种在各种恶性肿瘤中持续上调的致癌驱动因子，可作为预后和诊断的潜在通用生物标志物。其在调节免疫反应和预测治疗敏感性方面的关键作用突出了其在个性化癌症治疗策略中的重要性。HuR通过整体调节重要的细胞过程来协调肿瘤发生和恶性进展。
