A Prognostic lncRNA Signature Associated with Lipid Metabolism in Glioma

Abstract Background: Long noncoding RNAs (lncRNAs) are promising cancer biomarkers and therapeutic targets . And lipid metabolism reprogramming is a trait of cancer metabolism. However, the relationship between lncRNAs and lipid metabolism and their prognostic value are still unclear in glioma. Hence, we screened for prognostic lncRNAs associated with lipid metabolism and explored their potential biological functions and effects on glioma. Methods: The glioma data were obtained from TCGA and CGGA databases. Correlation analysis was used to identify the lncRNAs associated with lipid metabolism . The Cox and LASSO regression analysis were adopted to find prognostic lncRNAs, and further established ceRNA network, clustering and risk score models. CNV and somatic mutation data were used to explore the correlation between risk score and genomic alterations. GSVA and GSEA was adopted to reveal the potential biological functions of prognostic lncRNAs. The abundance of 22 immune cells was inferred by CIBERSORT algorithm . The TIDE algorithm and GDSC database were used to predict the patient's response to immunotherapy and chemotherapy, respectively. Human glioma cell lines were used for further experimental validation. CCK-8 and colony forming assays were adopted to evaluate the cell viability. The cell proliferation was detected by EdU assay. Transwell assay was used to evaluate the ability of cell invasion and migration. Results: A total of twenty prognostic lncRNAs associated with lipid metabolism were found, and a prognostic lncRNA signature was established. A high risk-score suggested a poor prognosis , more malignant clinicopathological and genomic aberrations features. The risk score was also an independent prognos tic factor. The high-risk patients were more likely to benefit from anti-PD1 treatment. The biological function of signature lncRNAs was mainly to regulate the biosynthesis and transportation of lipid (especially the fatty acid). Among signature lncRNAs, LINC01614 was associated with prognosis, genomic aberrations characteristics, m6A methylation modification, immune infiltration status, and chemotherapy response of patients with glioma. In vitro experiments, silencing the expression of LINC01614 could inhibit the viability, migration , and proliferation of glioma cells. Conclusions: A prognostic lncRNA signature containing twenty lncRNAs associated with lipid metabolism was established in glioma. The signature lncRNAs play an important role in the development of glioma by regulating lipid biosynthesis and transportation. Our study also provides a new perspective for understanding the lipid metabolism and the biological role of lncRNAs in glioma.