Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford, OX3 7FZ, UK.
J Transl Med. 2019 Jan 9;17(1):14. doi: 10.1186/s12967-019-1775-9.
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.
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).
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.
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.
尽管癌症研究取得了很大进展，但癌症的发病率和死亡率仍在继续上升。一个强大的生物标志物，可以预测肿瘤的行为，是非常理想的，它可以改善患者的治疗和预后。
在一项涉及 839 名肝癌患者的回顾性生物信息学分析中，我们开发了一个由 45 个与肿瘤浸润淋巴细胞和细胞对缺氧反应相关的基因组成的预后特征。从这个基因集，我们能够确定由 8 个基因组成的第二个预后特征。它在另外五种癌症中进一步得到验证：头颈部（n=520）、肾乳头细胞癌（n=290）、肺癌（n=515）、胰腺癌（n=178）和子宫内膜癌（n=370）。
45 个基因特征预测了三个肝癌队列的总生存率：风险比（HR）=1.82，P=0.006；HR=1.84，P=0.008 和 HR=2.67，P=0.003。此外，简化的 8 个基因特征足以有效地预测肝癌和其他五种癌症的生存情况：肝癌（HR=2.36，P=0.0003；HR=2.43，P=0.0002 和 HR=3.45，P=0.0007）、头颈部（HR=1.64，P=0.004）、肾乳头细胞癌（HR=2.31，P=0.04）、肺癌（HR=1.45，P=0.03）、胰腺癌（HR=1.96，P=0.006）和子宫内膜癌（HR=2.33，P=0.003）。受试者工作特征分析表明，这两个特征都优于当前的肿瘤分期参数。多变量 Cox 回归分析显示，这两个基因特征在这些癌症中都是独立于其他临床病理特征的。将基因特征与体细胞突变谱相结合，提高了它们的预后能力。
据我们所知，这项研究首次在六种癌症类型（n=2712）中确定了一个将肿瘤缺氧和淋巴细胞浸润结合起来作为预后决定因素的基因特征。该 8 个基因特征可通过纳入缺氧信息来帮助临床决策，用于患者的风险分层。
