IL-10 and PRKDC polymorphisms are associated with glioma patient survival.

Mingjun Hu,Jieli Du,Lihong Cui,Xiaoye Guo,Jinning Song,Yonglin Zhao,Tianbo Jin,Gang Li,Xudong Ma,Tingqin Huang

doi:10.18632/oncotarget.13028

Abstract

Interleukin-10 (IL-10) and DNA repair gene PRKDC mutations are implicated in the development of multiple human cancers, including glioma. We investigated associations between IL-10 and PRKDC gene polymorphisms and prognosis in low- and high-grade glioma patients. We analyzed the associations of one IL-10 and one PRKDC single nucleotide polymorphism with patient clinical factors in 481 glioma patients using Cox proportional hazard models and Kaplan-Meier curves. We also assessed associations between patient clinical characteristics and prognosis. Our data showed that the extent of tumor resection (gross-total resection) and application of chemotherapy were associated with improved patient outcomes in all glioma cases. Additionally, univariate (Log-rank p = 0.019) and multivariate Cox regression analyses (p = 0.022) showed that the IL-10 rs1800871 C/T genotype correlates with improved overall survival in cases of low-grade glioma, whereas the PRKDC rs7003908 C/C genotype correlated with reduced overall and progression-free survival in high-grade glioma patients in univariate (Log-rank p = 0.000 and p = 0.000, respectively) and multivariate Cox regression analyses (p = 0.001; p = 0.002, respectively). These results suggest that IL-10 rs1800871 and PRKDC rs7003908 may be useful biomarkers for predicting glioma patient outcome. Further functional studies are needed to evaluate the mechanisms by which these polymorphisms affect glioma progression.

Highlights

Glioma is a general term used to describe any tumor that arises from the supportive tissue of the brain
In a univariate analysis of clinical factors, including patient gender and age, extent of tumor resection, and radiotherapy and chemotherapy regimen, we found that the median overall survival (OS) of World Health Organization (WHO) grade I–II glioma patients (12 months; 3-year survival rate = 9.0%) was longer than that of WHO grade III–IV patients (10 months; 3-year survival rate = 5.5%) (Log-rank p = 0.039) (Tables 2–4)
We found that the PRKDC rs7003908 C/C genotype correlated with poor prognosis in high-grade glioma patients as measured by OS (3-year survival rate = 0.0%, median survival = 6 months, Log-rank p = 0.000, hazard ratios (HRs) = 4.556, 95% confidence intervals (CIs) = 1.936–10.721, p = 0.001) and PFS (3-year survival rate = 0.0%, median survival = 4 months, Log-rank p = 0.000, HR = 4.430, 95% CI = 1.884–10.416, p = 0.001), this was not observed in low-grade glioma patients

Summary

Introduction

Glioma is a general term used to describe any tumor that arises from the supportive (gluey) tissue of the brain. This tissue, called glia, helps to keep the neurons in place and functioning well. It is the most common and aggressive primary brain tumors, occurring most commonly in adults and accounting for 40–50% of all brain tumors [1]. Despite total or near-total tumor resection, and advancements in chemo-radiotherapy, patient outcomes remain dismal. Median survival times for patients with grade III and IV gliomas are only 39 and 30 weeks, respectively [4]

Methods

Results

Conclusion