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
作者: StephenW 时间: 2019-1-10 20:00
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