Clinical and Molecular Characterization of Incidentally Discovered Lower-Grade Gliomas with Enrichment of Aerobic Respiration

PURPOSE: Incidentally discovered diffusely infiltrating lower-grade gliomas (incidental LGGs, iLGGs) are defined as gliomas occasionally found in patients without tumor-related symptoms. At present, very few in-depth research studies on incidental LGGs were reported. We aimed to find out the inherent difference between iLGGs and LGGs with tumor-related symptoms. PATIENTS AND METHODS: We enrolled 2486 all-grade gliomas and screened 1594 lower-grade gliomas for further analysis. Medical records were retrospectively reviewed for iLGGs. Clinical and mRNA sequencing data were collected for in-depth analysis. RESULTS: We found that with increasing grade, the proportion of incidental glioma patients decreased obviously. In 1594 patients who underwent craniotomy for LGG, 80 (5%) patients were discovered incidentally. Grade II patients (88%) and patients bearing 1p/19q co-deletion in their tumors (23%) were more likely to be diagnosed as iLGGs. Regular radiological screening (48%) and trauma (24%) were the main complaint for brain imaging for iLGGs. Kaplan–Meier survival analysis indicated that iLGGs patients lived a significantly longer survival and Cox regression analysis revealed that iLGGs were an independent indicator of better prognosis. Subsequent gene set enrichment analysis and differential expression analysis based on the gene expression profile revealed that mitochondrial aerobic respiration process was enriched in iLGGs. Moreover, we found that iLGGs tended to generate energy by unique mitochondrial aerobic respiration. CONCLUSION: These results provided a primitive exploration of iLGGs, which may potentially assist clinical neurosurgeons with personalized management of iLGGs.