Revealing transcriptional and post-transcriptional regulatory mechanisms of γ-glutamyl transferase and keratin isoforms as novel cooperative biomarkers in low-grade glioma and glioblastoma multiforme.

ABSTRACT

Gamma-glutamyltransferase (GGT) and keratins (KRT) are key factors in regulating tumor progression rely on emerging evidence. However, the prognostic values of GGT and KRT isoforms and their regulation patterns at transcriptional and post-transcriptional levels have been rarely studied. In this study, we aimed to identify cooperative prognostic biomarker signature conducted by GGT and KRT genes for overall survival prediction and discrimination in patients with low-grade glioma (LGG) and glioblastoma multiforme (GBM). To this end, we employed a differential expression network analysis on LGG-NORMAL, GBM-NORMAL, and LGG-GBM datasets. Then, all the differentially expressed genes related to a GO term "GGT activity" were excluded. After that, for obtained potential biomarkers genes, differentially expressed lncRNAs were used to detect cis-regulatory elements (CREs) and trans-regulatory elements (TREs). To scrutinize the regulation on the cytoplasm, potential interactions between these biomarker genes and DElncRNAs were predicted. Our analysis, for the first time, revealed that GGT6, KRT33B, and KRT75 in LGG, GGT2, and KRT75 in GBM and KRT75 for LGG to GBM transformation tumors can be novel cooperative prognostic biomarkers that may be applicable for early detection of LGG, GBM, and LGG to GBM transformation tumors. Consequently, KRT75 was the most important gene being regulated at both transcriptional and post-transcriptional levels significantly. Furthermore, CREs and their relative genes were coordinative up-regulated or down-regulated suggesting CREs as regulation points of these genes. In the end, up-regulation of most DElncRNAs that had physical interaction with target genes pints out that the transcripted genes may have obstacles for translation process.