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双硫死亡相关基因影响预后及肿瘤微环境的泛癌分析

孙敬阳, 蒋荣轩, 侯理仁, 董欢欢, 林亦瀚, 董妞妞, 张广健, 张言鹏

孙敬阳, 蒋荣轩, 侯理仁, 董欢欢, 林亦瀚, 董妞妞, 张广健, 张言鹏. 双硫死亡相关基因影响预后及肿瘤微环境的泛癌分析[J]. 肿瘤防治研究, 2025, 52(1): 52-61. DOI: 10.3971/j.issn.1000-8578.2025.24.0302
引用本文: 孙敬阳, 蒋荣轩, 侯理仁, 董欢欢, 林亦瀚, 董妞妞, 张广健, 张言鹏. 双硫死亡相关基因影响预后及肿瘤微环境的泛癌分析[J]. 肿瘤防治研究, 2025, 52(1): 52-61. DOI: 10.3971/j.issn.1000-8578.2025.24.0302
SUN Jingyang, JIANG Rongxuan, HOU Liren, DONG Huanhuan, LIN Yihan, DONG Niuniu, ZHANG Guangjian, ZHANG Yanpeng. Pan-Cancer Analysis of Disulfidptosis-Related Genes Affecting Prognosis and Tumor Microenvironment[J]. Cancer Research on Prevention and Treatment, 2025, 52(1): 52-61. DOI: 10.3971/j.issn.1000-8578.2025.24.0302
Citation: SUN Jingyang, JIANG Rongxuan, HOU Liren, DONG Huanhuan, LIN Yihan, DONG Niuniu, ZHANG Guangjian, ZHANG Yanpeng. Pan-Cancer Analysis of Disulfidptosis-Related Genes Affecting Prognosis and Tumor Microenvironment[J]. Cancer Research on Prevention and Treatment, 2025, 52(1): 52-61. DOI: 10.3971/j.issn.1000-8578.2025.24.0302

双硫死亡相关基因影响预后及肿瘤微环境的泛癌分析

基金项目: 国家自然科学基金(82103467);西安交通大学基础医学-临床整合创新项目(YXJLRH2022033)
详细信息
    作者简介:

    孙敬阳,男,硕士,住院医师,主要从事胸部肿瘤及肺移植的临床与转化研究,ORCID: 0009-0001-9941-8284

    通信作者:

    张言鹏,男,博士,助理研究员,主要从事肺部恶性肿瘤与肺移植的基础及临床转化研究,E-mail: yanpeng_zhang@xjtu.edu.cn,ORCID: 0009-0000-4975-4418

  • 中图分类号: R73

Pan-Cancer Analysis of Disulfidptosis-Related Genes Affecting Prognosis and Tumor Microenvironment

Funding: National Natural Science Foundation of China (No. 82103467); Basic Medicine and Clinical Integration Innovation Project of Xi’an Jiaotong University (No. YXJLRH2022033)
More Information
  • 摘要:
    目的 

    基于生物信息学方法评估双硫死亡相关基因(DRGs)在泛癌中对预后及免疫的潜在作用。

    方法 

    使用TCGA及多种开源在线数据库内包含的泛癌RNA-seq数据、突变情况、临床信息、TMB、MSI、干性评分和肿瘤及免疫微环境数据及多组R语言算法综合分析。使用qPCR对细胞层面的DRGs表达情况行实验验证。

    结果 

    LRPPRC、NCKAP1、NDUFS1和NUBPL在肾透明细胞癌中的预后较好(P<0.001),而 SLC7A11、NCKAP1和SLC3A2在肝细胞癌中的预后较差(P<0.01)。在TME分析中,LRPPRC与所有肿瘤类型中的免疫细胞、基质细胞和估计评分均呈负相关。TMB分析结果揭示了DRGs在泛癌中PD-1/PD-L1治疗的潜在研究价值。药物敏感性分析发现SLC7A11(r=0.454)、SLC3A2(r=0.366)和NCKAP1(r=0.455)与Kahalide F明显相关(P<0.01)。实验验证表明了GYS1与NCKAP1在肺腺癌、结肠腺癌、食管鳞癌与肝细胞癌中总体表达高于正常细胞,且存在差异(P<0.05)。

    结论 

    通过对DRGs的泛癌分析表明,DRGs可能作为肾透明细胞癌、肺腺癌、肝细胞癌诊断及预后的重要生物标志物。

     

    Abstract:
    Objective 

    To assess the potential role of disulfidptosis-related genes (DRGs) in pan-cancer on prognosis and immunity on the basis of bioinformatics approaches.

    Methods 

    Pan-cancer RNA-seq data, mutation profiles, clinical information, TMB, MSI, stemness scores, and tumor and immune microenvironment data contained in TCGA and various open-source online databases, and multi-group R-language algorithms were used for comprehensive analysis. The expression levels of DRGs at the cellular level were experimentally validated using qPCR.

    Results 

    LRPPRC, NCKAP1, NDUFS1, and NUBPL had a better prognosis in renal clear cell carcinoma (P<0.001), whereas SLC7A11, NCKAP1, and SLC3A2 had a worse prognosis in hepatocellular carcinoma (P<0.001). TME analysis showed that LRPPRC was negatively correlated with immune cells, stromal cells, and estimated scores in all tumor types. TMB analysis revealed the potential research value of DRGs for PD-1/PD-L1 therapy in pan-cancer. Drug sensitivity analysis showed that SLC7A11 (r=0.454), SLC3A2 (r=0.366), and NCKAP1 (r=0.455) were significantly associated with Kahalide F (P<0.01). Experimental validation demonstrated the overall higher expression levels of GYS1 and NCKAP1 than normal cells in lung adenocarcinoma, colon adenocarcinoma, esophageal squamous carcinoma, and hepatocellular carcinoma (P<0.05).

    Conclusion 

    Pan-cancer analysis of DRGs indicates that DRGs may serve as important biomarkers for the diagnosis and prognosis of renal clear-cell carcinoma, lung adenocarcinoma, and hepatocellular carcinoma.

     

  • Competing interests: The authors declare that they have no competing interests.
    利益冲突声明:
    所有作者均声明不存在利益冲突。
    作者贡献:
    孙敬阳:文章写作、数据分析
    蒋荣轩、侯理仁、董欢欢:数据整理及管理
    林亦瀚、董妞妞:数据可视化分析
    张广健:研究设计
    张言鹏:研究设计、基金项目负责人
  • 图  3   双硫死亡相关基因的表达与泛癌免疫和肿瘤微环境之间的相关性

    Figure  3   Correlation among DRG expression, pan-cancer immune and tumor microenvironment

    图  4   双硫死亡相关基因的肿瘤突变负荷与微卫星不稳定性分析

    Figure  4   Analysis of TMB and MSI of DRGs

    图  5   泛癌中DRGs药物敏感性分析

    Figure  5   Sensitivity analysis of DRG drugs in pan-cancer

    图  6   双硫死亡相关基因与特定肿瘤类型的微环境和干细胞评分的相关性

    Figure  6   Correlation among DRGs, specific tumor types’ microenvironment and stem score

    图  7   TCGA公共数据与PCR细胞系中结肠腺癌、肺腺癌、肝细胞癌、食管鳞癌中GYS1与NCKAP1的表达差异

    Figure  7   Expression differences of GYS1 and NCKAP1 in colon adenocarcinoma, lung adenocarcinoma, hepatocellular carcinoma, and esophageal squamous carcinoma in PCR cell lines and TCGA public data

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出版历程
  • 收稿日期:  2024-04-03
  • 修回日期:  2024-06-15
  • 录用日期:  2024-10-20
  • 网络出版日期:  2024-10-30
  • 刊出日期:  2025-01-24

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