来自免疫调节和缺氧基因的新特征预测肝脏和其他五种癌症

StephenW

A novel signature derived from immunoregulatory and hypoxia genes predicts prognosis in liver and five other cancers

    Wai Hoong Chang, Donall Forde and Alvina G. LaiEmail authorView ORCID ID profile

Journal of Translational Medicine201917:14

https://doi.org/10.1186/s12967-019-1775-9

©  The Author(s) 2019

    Received: 13 October 2018Accepted: 4 January 2019Published: 9 January 2019

Abstract
Background

Despite much progress in cancer research, its incidence and mortality continue to rise. A robust biomarker that would predict tumor behavior is highly desirable and could improve patient treatment and prognosis.
Methods

In a retrospective bioinformatics analysis involving patients with liver cancer (n = 839), we developed a prognostic signature consisting of 45 genes associated with tumor-infiltrating lymphocytes and cellular responses to hypoxia. From this gene set, we were able to identify a second prognostic signature comprised of 8 genes. Its performance was further validated in five other cancers: head and neck (n = 520), renal papillary cell (n = 290), lung (n = 515), pancreas (n = 178) and endometrial (n = 370).
Results

The 45-gene signature predicted overall survival in three liver cancer cohorts: hazard ratio (HR) = 1.82, P = 0.006; HR = 1.84, P = 0.008 and HR = 2.67, P = 0.003. Additionally, the reduced 8-gene signature was sufficient and effective in predicting survival in liver and five other cancers: liver (HR = 2.36, P = 0.0003; HR = 2.43, P = 0.0002 and HR = 3.45, P = 0.0007), head and neck (HR = 1.64, P = 0.004), renal papillary cell (HR = 2.31, P = 0.04), lung (HR = 1.45, P = 0.03), pancreas (HR = 1.96, P = 0.006) and endometrial (HR = 2.33, P = 0.003). Receiver operating characteristic analyses demonstrated both signatures superior performance over current tumor staging parameters. Multivariate Cox regression analyses revealed that both 45-gene and 8-gene signatures were independent of other clinicopathological features in these cancers. Combining the gene signatures with somatic mutation profiles increased their prognostic ability.
Conclusions

This study, to our knowledge, is the first to identify a gene signature uniting both tumor hypoxia and lymphocytic infiltration as a prognostic determinant in six cancer types (n = 2712). The 8-gene signature can be used for patient risk stratification by incorporating hypoxia information to aid clinical decision making.
Keywords

    Hypoxia
    T cells
    Tumor-infiltrating lymphocytes
    Hepatocellular carcinoma
    Pan-cancer
    Gene signature

StephenW

来自免疫调节和缺氧基因的新特征预测肝脏和其他五种癌症的预后

    Wai Hoong Chang，Donall Forde和Alvina G. LaiEmail authorView ORCID ID profile

转化医学杂志201917：14

https://doi.org/10.1186/s12967-019-1775-9

©作者2019

    收稿日期：2018年10月13日接受日期：2019年1月4日出版日期：2019年1月9日

抽象
背景

尽管癌症研究取得了很大进展，但其发病率和死亡率仍在上升。预测肿瘤行为的稳健生物标志物是非常需要的并且可以改善患者治疗和预后。
方法

在一项涉及肝癌患者的回顾性生物信息学分析中（n = 839），我们开发了一个预后标记，由45个与肿瘤浸润淋巴细胞相关的基因和细胞对缺氧的反应组成。从该基因组中，我们能够鉴定出由8个基因组成的第二个预后特征。其性能在其他五种癌症中得到进一步验证：头颈部（n = 520），肾乳头状细胞（n = 290），肺（n = 515），胰腺（n = 178）和子宫内膜（n = 370）。
结果

45基因特征预测了三个肝癌队列的总体存活率：风险比（HR）= 1.82，P = 0.006; HR = 1.84，P = 0.008，HR = 2.67，P = 0.003。此外，减少的8基因特征足以有效地预测肝脏和其他五种癌症的存活率：肝脏（HR = 2.36，P = 0.0003; HR = 2.43，P = 0.0002和HR = 3.45，P = 0.0007），头部和颈部（HR = 1.64，P = 0.004），肾乳头状细胞（HR = 2.31，P = 0.04），肺（HR = 1.45，P = 0.03），胰腺（HR = 1.96，P = 0.006）和子宫内膜（HR） = 2.33，P = 0.003）。接受者操作特征分析证明两种特征都优于当前肿瘤分期参数。多变量Cox回归分析显示，45个基因和8个基因的特征与这些癌症中的其他临床病理学特征无关。将基因特征与体细胞突变谱相结合，增加了它们的预后能力。
结论

据我们所知，这项研究首次确定了将肿瘤缺氧和淋巴细胞浸润联合作为六种癌症类型（n = 2712）的预后决定因素的基因标记。通过引入缺氧信息以帮助临床决策，8基因特征可用于患者风险分层。
关键词

    缺氧
    T细胞
    肿瘤浸润淋巴细胞
    肝细胞癌
    泛癌
    基因签名

StephenW

https://translational-medicine.b ... 6/s12967-019-1775-9