Year: 2016
Type: conference-abstract
Abstract: Growing evidence is revealing an association between the myeloid cell infiltration and glioma development and progression. Therefore, identifying myeloid-derived genes variants that predict survival may demonstrate important insight into tumor biology and treatment. We evaluated 1878 single-nucleotide polymorphisms (SNPs) in 96 myeloid-derived genes for prognostic impact in 662 glioblastoma multiforme (GBM) and 562 low-grade gliomas (LGG), respectively, using Cox regression model. We then tested our promising findings in another independent datasets totaling 347 GBM and 667 LGG. The median survival time (MST) for GBM patients were 1.42 year; for LGG patients were 5.63 year. We identified 22 SNPs as predictors of GBM survival and 19 SNPs as predictors of LGG survival. For GBM, the strongest associations were attained at KCNN2 rs2974491 (HR 1.18; CI:1.05-1.35; p= 0.010), IL6 [rs6461667 (HR 0.84; CI:0.74-0.94; p=0.003), rs1554606 (HR 0.85; CI:0.75-0.95; p=0.007), and rs6954897 (HR 1.17; CI 1.06-1.31; p=0.0011)], and TLR4 [rs2149361 (HR 1.28; CI:1.08-1.51; p=0.003) and rs3860141 (HR 1.19; CI:1.03-1.30; p=0.010)]; for LGG, the strongest signals were seen at IL12A [rs2561287 (HR 1.41; CI:1.09-1.82; p=0.009), rs7610160 (HR 0.80; CI:0.67-0.95; p=0.010), and rs2366408 (HR 0.77; CI:0.66-0.95; p=0.14)], and IL17A rs17640030 (HR 1.42; CI: 1.12-1.92; p=0.009). These findings were further confirmed in the validation set and further joint effect analysis showed a strong gene-dosage effect for both GBM and LGG (Ptrend < 0.0001). The MST decreased progressively as the number of at-risk SNPs increased. This exploratory analysis supports polymorphisms in myeloid-derived genes, in particular, KCNN2, IL6 and TLR4 impacting GBM survival, and IL12A and IL17Agenes associated with LGG survival.
Source: Neuro-Oncology
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2587336663