1. Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
2. Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate, National Health and Family Planning Commission, Fuzhou, Fujian, China.
3. State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Rui-Jin Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
* These authors equally contributed to this work.
Objective: To analyze the prognostic effects of age in different tumor types and determine the prognostic significance of age related genes in patients with lower grade glioma (LGG).
Methods: The relationships between age and tumor overall survival were determined by Kaplan-Meier survival analysis using The Cancer Genome Atlas (TCGA) dataset. The age related genes were identified using TCGA RNA-seq data. Univariate and multivariate cox regression were used to determine the prognostic significance of age related genes. The results derived from TCGA dataset were further validated using Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) datasets.
Results: Age at initial pathologic diagnosis was most associated with the overall survival of LGG patients than other types of tumor patients. Age related genes EMP3, IGFBP2, TIMP1 and SERPINE1 were highly expressed in old LGG patients. The hypo-methylations of EMP3 and SERPINE1 were contributing to the high expressions of EMP3 and SERPINE1 in old LGG patients. Also, EMP3, IGFBP2, TIMP1 and SERPINE1 were highly expressed in LGG tumor tissues, compared with normal brain tissues. Moreover, high expressions of IGFBP2, EMP3, TIMP1 and SERPINE1 were associated with the worse prognosis of LGG patients. Furthermore, we demonstrated that EMP3 and SERPINE1 were connected with each other and the combination of EMP3 and SERPINE1 had better prognostic effects in glioma patients.
Conclusions: Age related genes IGFBP2, EMP3, TIMP1 and SERPINE1 have significant prognostic effects in LGG patients.
Keywords: Age related genes, Lower grade glioma, EMP3, SERPINE1, TCGA