1p19q Gene Transcription Profiles Closely Correlated to Malignancy and Prognosis of 1p/19q Non-Codeletion Gliomas

Abstract

Background: Co-deletion of chromosome arms 1p and 19q in oligodendroglial tumors is associated with chemosensitivity and favorable prognosis. Here, we explored the prognostic value of the expression of a panel of 1p19q genes in 1p/19q non-codeletion gliomas. Methods: We analyzed expression of 1p19q genes in 668 1p/19q non-codel gliomas obtained from The Cancer Genome Atlas (TCGA) (n = 447) and the Chinese Glioma Genome Atlas (CGGA) (n = 221) for training and validation, respectively. Least Absolute Shrinkage and Selection Operator Cox regression analysis was applied to build a gene risk signature. Results: Expression of 1p19q genes was significantly associated with the overall survival of patients with 1p/19q non-codel gliomas. We derived a risk signature of 25 selected 1p19q genes that successfully stratified the overall survival of 1p/19q non-codel glioma patients in both the TCGA and CGGA datasets into high- and low-risk groups (both P < 0.0001). Bioinformatics analysis revealed that the signature genes were significantly enriched in cell division, extracellular matrix, angiogenesis, DNA damage repair, and immune or inflammatory response processes, and these were supported by the immunohistochemistry. The risk signature not only predicted the chemoradiotherapeutic outcomes of glioblastoma and WHO grade III glioma patients but was also an independent prognostic marker for patients with 2016 WHO integrated diagnosis glioma subtypes. Conclusion: A risk signature consisting of 25 1p19q genes identified high-risk and low-risk categories of 1p/19q non-codel gliomas. This signature may be helpful for developing potential treatments strategies for these patients. Funding Statement: This work was supported by the National Natural Science Foundation of China (81773208, 81402052); the Beijing Nova Program (Z16110004916082); the National Key Research and Development Plan (2016YFC0902500). Declaration of Interests: The authors declare: none. Ethics Approval Statement: This study was approved by the institutional review board of Beijing Tiantan Hospital.