LncRNA HOTAIR Promotes Tumorigenicity in Glioblastoma

Abstract

Background Recently, the 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition) was published. WHO CNS5 incorporates numerous molecular changes to the accurate classification of CNS neoplasms. GBM, as a special type of glioma, is confined to IDH-wildtype in WHO CNS5, which has a short medical history and poor prognosis. LncRNA HOTAIR has been found to be responsible for the poor prognosis of several human cancers in previous studies. The clinical significance, the prognostic and treatment value of HOTAIR for GBM in the new WHO CNS5 classification remain unclear.Methods We created a Random Forest-based prediction model to assess the IDH1 mutational status of patients in REMBRANDT cohorts. Then we analyzed the role and the potential mechanism of HOTAIR in TCGA, CGGA, and REMBRANDT cohorts. GSVA and GSEA analysis were used to detect the potential biological functions and signaling pathways. The infiltration of immune cells was quantified by Cibersort. The effectiveness of targeted therapy in the clinical application was sought through drug response analysis. Furthermore, we verified that HOTAIR affected the proliferative activity of that glioma cells.Results We found that HOTAIR is highly expressed in all cohorts. The patients’ samples with high HOTAIR expression have poorer overall survival. The results of the functional analysis indicated that the cell cycle and proliferation-related processes were enriched in the high HOTAIR expression group. The infiltration of immunocytes is different in the two groups. In multiple immune checkpoints, the risk score showed a strong correlation. The analysis of drug treatment response present that the high HOTAIR expression group has a better treatment response and better curative effect on the treatment of temozolomide, sorafenib, lenalidomide, bexarotene, and axitinib.ConclusionIn conclusion, We found that HOTAIR could lead to poor prognosis of GBM mainly through regulation of cell cycle and apoptosis. And HOTAIR could be used as a marker to guide chemotherapy in GBM patients rather than immunocheckpoint inhibitor therapy.