Zhao Ligang, Jin Xiaoling, Yu Qiushi, He Yigang, Yang Facai, Ma Weihu, Lei Zhengqing, Zhou Jiahua
Hepato-Pancreato-Biliary Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Eur J Med Res. 2025 Aug 6;30(1):719. doi: 10.1186/s40001-025-02997-3.
This study sought to comprehensively examine PPP1R14B's function and its immune-related correlations in hepatocellular carcinoma (HCC).
RNA-seq and clinical information for HCC were procured from TCGA database. The links between PPP1R14B level and immune modulators plus immune cell populations were examined through Spearman correlation assessment. The immune landscape was assessed utilizing CIBERSORT and ESTIMATE algorithms. Gene set variation examination helped explore immune cell populations and their activities. The construction of prognostic models involved univariate and multivariate Cox regression investigations. Immunotherapy response and drug sensitivity were evaluated based on tumor immune dysfunction and exclusion (TIDE) and genomics of drug sensitivity in cancer (GDSC), respectively.
PPP1R14B levels were substantially elevated in HCC specimens versus normal tissues, and elevated expression independently linked to diminished survival rates. PPP1R14B levels exhibited notable associations with various immune cells, including memory B lymphocytes, M1/M2 macrophage populations, CD8-positive T lymphocytes, and T follicular helper cells. The analysis revealed distinct variations in immune scores and multiple immune cell enrichment patterns between elevated and reduced PPP1R14B expression categories, suggesting immune status connections. Elevated PPP1R14B cohorts demonstrated increased TIDE scores, alongside decreased IC50 measurements for specific drugs, including temsirolimus, sorafenib, rapamycin, dasatinib, and cytarabine, pointing to treatment response relationships. The study constructed a PPP1R14B-linked immune prediction model, demonstrating acceptable prognostic capability for HCC patients. The incorporation of pathological grade and pathological T stage parameters alongside risk scores in a nomogram enhanced the predictive accuracy.
This investigation thoroughly uncovered the significance of PPP1R14B in HCC, and established a PPP1R14B-linked immune prognostic signature. The findings facilitate the classification of HCC patients into distinct cohorts for developing individualized therapeutic approaches.
本研究旨在全面探讨PPP1R14B在肝细胞癌(HCC)中的功能及其与免疫相关的关联。
从TCGA数据库获取HCC的RNA测序数据和临床信息。通过Spearman相关性评估来研究PPP1R14B水平与免疫调节因子以及免疫细胞群体之间的联系。利用CIBERSORT和ESTIMATE算法评估免疫格局。基因集变异分析有助于探索免疫细胞群体及其活性。预后模型的构建涉及单变量和多变量Cox回归分析。分别基于肿瘤免疫功能障碍和排除(TIDE)以及癌症药物敏感性基因组学(GDSC)评估免疫治疗反应和药物敏感性。
与正常组织相比,HCC标本中PPP1R14B水平显著升高,且表达升高与生存率降低独立相关。PPP1R14B水平与多种免疫细胞存在显著关联,包括记忆B淋巴细胞、M1/M2巨噬细胞群体、CD8阳性T淋巴细胞和T滤泡辅助细胞。分析显示,PPP1R14B表达升高和降低的类别之间,免疫评分和多种免疫细胞富集模式存在明显差异,提示存在免疫状态关联。PPP1R14B水平升高的队列显示TIDE评分增加,同时包括替西罗莫司、索拉非尼、雷帕霉素、达沙替尼和阿糖胞苷在内的特定药物的IC50测量值降低,表明存在治疗反应关系。该研究构建了一个与PPP1R14B相关的免疫预测模型,对HCC患者显示出可接受的预后能力。在列线图中纳入病理分级和病理T分期参数以及风险评分提高了预测准确性。
本研究全面揭示了PPP1R14B在HCC中的重要性,并建立了一个与PPP1R14B相关的免疫预后特征。这些发现有助于将HCC患者分类为不同队列,以制定个性化治疗方案。