BACKGROUND: Lower-grade gliomas (LGGs) vary widely in terms of the patient’s overall survival (OS). There is no current, valid method that could exactly predict the survival. The effects of intratumoral immune infiltration on clinical outcome have been widely reported. Thus, we aim to develop an immune infiltration signature to predict the survival of LGG patients. METHODS: We analyzed 1216 LGGs from 5 public data sets, including 2 RNA sequencing data sets and 3 microarray data sets. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select an immune infiltration signature and build a risk score. The performance of the risk score was assessed in the training set (329 patients), internal validation set (140 patients), and 4 external validation sets (405, 118, 88, and 136 patients). RESULTS: An immune infiltration signature consisting of 20 immune metagenes was used to generate a risk score. The performance of the risk score was thoroughly verified in the training and validation sets. Additionally, we found that the risk score was positively correlated with the expression levels of TGF-β and PD-L1, which were important targets of combination immunotherapy. Furthermore, a nomogram incorporating the risk score, patient’s age, and tumor grade was developed to predict the OS, and it performed well in all the training and validation sets (C-index: 0.873, 0.881, 0.781, 0.765, 0.721, and 0.753). CONCLUSION: The risk score based on the immune infiltration signature has reliable prognostic and predictive value for patients with LGGs and is a potential biomarker for the cotargeting immunotherapy. FUNDING: This work was supported by The National Natural Science Foundation of China (grant nos. 81472370 and 81672506), the Natural Science Foundation of Beijing (grant no. J180005), the National High Technology Research and Development Program of China (863 Program, grant no. 2014AA020610), and the National Basic Research Program of China (973 Program, grant no. 2014CB542006).

Serpin family F member 1 (SERPINF1) reportedly plays multiple roles in various tumors; however, its clinical significance and molecular functions in glioma have been largely understudied. In the present study, we analyzed the prognostic value of SERPINF1 in three independent glioma datasets. Next, we explored the molecular functions and transcriptional regulation of SERPINF1 at the single-cell level. Moreover, in vitro experiments were conducted to evaluate the roles of SERPINF1 in the proliferation, invasion, migration, and stemness of glioma cells. Our results showed that a higher expression of SERPINF1 correlated with a poor overall survival rate in glioma patients (hazard ratio: 4.061 in TCGA, 2.017 in CGGA, and 1.675 in GSE16011, p < 0.001). Besides, SERPINF1 knockdown could suppress the proliferation, invasion, and migration of glioma cells in vitro. In addition, SERPINF1 expression was significantly upregulated in glioma stem cells (GSCs) compared to parental glioma cells. Knocking down SERPINF1 impaired the sphere formation of GSC-A172 and GSC-LN18. Bioinformatics analysis revealed that Notch signaling activation was closely associated with high SERPINF1 expression at the single-cell level. Furthermore, STAT1, CREM, and NR2F2 may participate in the transcriptional regulation of SERPINF1 in glioma. Overall, our results suggest that SERPINF1 may be a candidate prognostic predictor and potential therapeutic target for glioma.

Objective: Intracranial pineoblastomas are rare neoplasms with poor prognosis. The aim of this study was to describe the independent prognostic factors and treatment strategies for overall survival in pediatric and adult patients. Methods: Sixty-four patients were surgically treated between January 2012 and December 2018. Results: The series included 37 (57.8%) males and 27 (42.2%) females. Gross total resection was achieved in 41 (64.1%) cases, and the 1-, 3-, and 5-year rates of overall survival were 86.3, 52.3, and 36.6%, respectively. In the pediatric group (n=42), 28 patients (66.7%) were male, with the median, and the mean age was 4 and 6.2± 4.7 years, respectively. After a median follow-up of 25.0 months, twenty-six patients (61.9%) died, and the 1-, 3-, and 5-year rates of overall survival were 84.9, 46.4, and 26.7%, respectively. Postoperative radiotherapy (p=0.058) and postoperative chemotherapy (p=0.183) had a positive influence on the increased overall survival. Meanwhile, postoperative radiotherapy combined with chemotherapy following surgery had a positive impact on overall survival (p=0.174, Log rank). In the adult group, the mean overall survival was 67.3± 9.3 months (range, 0.8– 95.3 months), and the 1-, 3-, and 5-year rates of overall survival were 89.5, 64.4, and 64.4%, respectively. In this group, no statistical association was observed between clinical factors and outcomes. However, patients who received postoperative radiotherapy (60.7 vs 57.6 month, mean survival; p=0.510, Log rank) or chemotherapy (63.0 vs 59.9 month, mean survival; p=0.404, Log rank) had better survival rates compared with those who declined. Conclusion: In the pediatric group, surgery with postoperative radiotherapy and chemotherapy was a favorable factor for overall survival. In the adult group, a positive trend in overall survival was found when patients received radiation and/or chemotherapy following surgery.

The presence of TERTp mutation in isocitrate dehydrogenase-wildtype (IDHwt) histologically lower-grade glioma (LGA) has been linked to a poor prognosis. In this study, we aimed to develop and validate a radiomic nomogram based on multimodal MRI for predicting TERTp mutations in IDHwt LGA. One hundred and nine IDH wildtype glioma patients (TERTp-mutant, 78; TERTp-wildtype, 31) with clinical, radiomic, and molecular information were collected and randomly divided into training and validation set. Clinical model, fusion radiomic model, and combined radiomic nomogram were constructed for the discrimination. Radiomic features were screened with 3 algorithms (Wilcoxon rank sum test, elastic net, and the recursive feature elimination) and the clinical characteristics of combined radiomic nomogram were screened by the Akaike information criterion. Finally, receiver operating characteristic curve, calibration curve, Hosmer–Lemeshow test, and decision curve analysis were utilized to assess these models. Fusion radiomic model with 4 radiomic features achieved an area under the curve value of 0.876 and 0.845 in the training and validation set. And, the combined radiomic nomogram achieved area under the curve value of 0.897 (training set) and 0.882 (validation set). Above that, calibration curve and Hosmer–Lemeshow test showed that the radiomic model and combined radiomic nomogram had good agreement between observations and predictions in the training set and the validation set. Finally, the decision curve analysis revealed that the 2 models had good clinical usefulness for the prediction of TERTp mutation status in IDHwt LGA. The combined radiomics nomogram performed great performance and high sensitivity in prediction of TERTp mutation status in IDHwt LGA, and has good clinical application.

Background: Identifying a unique and common regulatory pathway that drives tumorigenesis in cancers is crucial to foster the development of effective treatments. However, a systematic analysis of fatty acid synthase across pan-cancers has not been carried out. Methods: We investigated the oncogenic roles of fatty acid synthase in 33 cancers based on the cancer genome atlas and gene expression omnibus. Results: Fatty acid synthase is profoundly expressed in most cancers and is an important factor in predicting the outcome of cancer patients. Further, the level of S207 phosphorylation was found to be improved in several neoplasms (e.g., colon cancer). Fatty acid synthase expression is related to tumor-infiltrating immune cells in tumors (e.g., CD8(+) T-cell infiltration level in cervical squamous cell carcinoma). Moreover, hormone receptor binding- and fatty acid metabolic process-associated pathways are involved in the functional mechanisms of fatty acid synthase. Conclusions: This study provides a complete understanding of the oncogenic role of fatty acid synthase in human tumors.

Meningioma was the most primary intracranial tumor, but the molecular characteristics and the treatment of malignant meningioma were still unclear. Nine malignant progression-related genes based prognostic signatures were identified by transcriptome analysis between benign meningioma and malignant meningioma. The external dataset GEO136661 and quantitative Real-time Polymerase Chain Reaction were used to verify the prognostic factors. has-miR-3605-5p, hsa-miR-664b-5p, PNRC2, BTBD8, EXTL2, SLFN13, DGKD, NSD2, and BVES were closed with malignant progression. Moreover, Doxorubicin was identified by Connectivity Map website with the differential malignant progression-related genes. CCK-8 assay, Edu assay, wound healing assay, and trans-well experiment were used to reveal that Doxorubicin could inhibit proliferation, migration and invasion of IOMM-Lee Cells.