Inflammation is related to cancer. The systemic immune-inflammation index (SII) has been linked to the prognosis of many types of cancer. The present study aimed to determine the prognostic value of the SII in glioblastoma (GBM) patients based on meta-analysis and single-center retrospective analysis. Relevant publications published before 1 October 2022 were identified by searching PubMed, EMBASE, Cochrane Library databases, and Web of Science. Moreover, 208 GBM patients from Zhongnan Hospital were incorporated. Kaplan–Meier and Cox regression analyses determined the prognostic significance of inflammatory markers. By combining these indicators, we developed scoring systems. Nomograms were also built by incorporating independent variables. The accuracies of nomograms were evaluated by Harrell’s concordance index (c-index) and the calibration curve. According to meta-analysis, an elevated SII predicted the worst overall survival (OS) (Hazard ratio [HR] = 1.87, p < 0.001). Furthermore, a higher SII (>510.8) (HR = 1.782, p = 0.007) also predicted a poorer outcome in a retrospective cohort. The scoring systems of SII-NLR (neutrophil-to-lymphocyte ratio) showed the best predictive power for OS. The nomogram without MGMT (c-index = 0.843) exhibited a similar accuracy to that with MGMT (c-index = 0.848). A pre-treatment SII is independently associated with OS in GBM. A nomogram integrating the SII-NLR score may facilitate a comprehensive survival evaluation independent of molecular tests in GBM.

Backgroud: HOX transcript antisense RNA (HOTAIR) is upregulated in glioblastoma (GBM) and associated with temozolomide (TMZ) resistance. However, the mechanisms underlying HOTAIR-mediated TMZ resistance remains poorly understood. Methods HOTAIR expression in glioma-related public datasets and drug response estimation were analyzed using bioinformatics. These findings were verified by overexpressing HOTAIR in TMZ-sensitive U251 cells and/or silencing HOTAIR in resistant U251 cells (U251R). The cytotoxic effects were evaluated using cell viability assay and flow cytometry analysis of cell clycle and apoptosis. Results HOTAIR was upregulated in TMZ-resistant GBM cell lines and patients with high HOTAIR expression responded poorly to TMZ therapy. HOTAIR knockdown restored TMZ sensitivity in U251R cells, while HOTAIR overexpression conferred TMZ resistance in U251 cells. Wnt/β-catenin signaling was enriched in patients with high HOTAIR expression; consistently, HOTAIR positively regulated β-catenin expression in U251 cells. Moreover, HOTAIR-mediated TMZ resistance was associated with increased MGMT protein level, which resulted from the HOTAIR/miR-214-3p/β-catenin network. GBM with high HOTAIR expression exhibited sensitivity to methotrexate. Methotrexate enhanced TMZ sensitivity in U251R cells, accompanied by reduced expression of HOTAIR and β-catenin. Conclusions HOTAIR is a risk factor for TMZ resistance and methotrexate may represent a potential therapeutic drug for patients with high HOTAIR expression level.