Integrative analyses identify a DNA damage repair gene signature for prognosis prediction in lower grade gliomas.

Background: The DNA damage repair (DDR) pathways play important roles for regulating cancer progression and therapeutic response. IDH mutations, well-known prognosis biomarkers for glioma, lead to hypermethylation of tumor cells and affect genes' expression. Whether IDH mutations affect glioma prognosis through influencing the expression of DDR genes remains unclear. Methods: A total of 272 DDR genes were selected for differential expression and survival analysis. The identified genes were then utilized to construct the prognosis predicting model. Results: PARPBP, PLK3, POLL and WEE1 were found differential expressed between IDH mutations carriers and wild-type carriers, and were associated with survival of low grade glioma (LGG) patients. The predicting algorithm can predicts the prognosis of LGG patients. Conclusion: IDH mutations may affect LGG prognosis through regulation of DDR pathways.

Overexpression of Fn14 in gliomas: tumor progression and poor prognosis.

AIM: To confirm whether the expression level of Fn14 could affect progression or prognosis of glioma patients. METHODS: Glioma cohorts in The Cancer Genome Atlas, Gene Expression Omnibus and Chinese Glioma Genome Atlas databases were comprehensively analyzed. RESULTS: Low-grade patients had lower expression level of Fn14, while patients with higher expression of Fn14 tended to harbor shorter overall survival and disease-free survival. The expression level of Fn14 was downregulated by IDH1/IDH2 mutations while its gene body methylation was upregulated. After adjusting age, the expression level of Fn14 was still significantly associated with overall survival and disease-free survival in low-grade gliomas. In a cell line data analysis, Fn14 expression was positively correlated with temozolomide dosage. CONCLUSION: Fn14 was an independent predictive biomarker for the progression and prognosis in low-grade gliomas.

Association of a cytarabine chemosensitivity related gene expression signature with survival in cytogenetically normal acute myeloid leukemia.

The prognosis of cytogenetically normal acute myeloid leukemia (CN-AML) varies greatly among patients. Achievement of complete remission (CR) after chemotherapy is indispensable for a better prognosis. To develop a gene signature predicting overall survival (OS) in CN-AML, we performed data mining procedure based on whole genome expression data of both blood cancer cell lines and AML patients from open access database. A gene expression signature including 42 probes was derived. These probes were significantly associated with both cytarabine half maximal inhibitory concentration values in blood cancer cell lines and OS in CN-AML patients. By using cox regression analysis and linear regression analysis, a chemo-sensitive score calculated algorithm based on mRNA expression levels of the 42 probes was established. The scores were associated with OS in both the training sample (p=5.13 × 10-4, HR=2.040, 95% CI: 1.364-3.051) and the validation sample (p=0.002, HR=2.528, 95% CI: 1.393-4.591) of the GSE12417 dataset from Gene Expression Omnibus. In The Cancer Genome Atlas (TCGA) CN-AML patients, higher scores were found to be associated with both worse OS (p=0.013, HR=2.442, 95% CI: 1.205-4.950) and DFS (p=0.015, HR=2.376, 95% CI: 1.181-4.779). Results of gene ontology (GO) analysis showed that all the significant GO Terms were correlated with cellular component of mitochondrion. In summary, a novel gene set that could predict prognosis of CN-AML was identified presently, which provided a new way to identify genes impacting AML chemo-sensitivity and prognosis.