A TGF-ß signaling-related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response.

AIMS: The dysregulation of TGF-ß signaling is a crucial pathophysiological process in tumorigenesis and progression. LncRNAs have diverse biological functions and are significant participants in the regulation of tumor signaling pathways. However, the clinical value of lncRNAs related to TGF-ß signaling in glioma is currently unclear. METHODS: Data on glioma's RNA-seq transcriptome, somatic mutation, DNA methylation data, and clinicopathological information were derived from the CGGA and TCGA databases. A prognostic lncRNA signature was constructed by Cox and LASSO regression analyses. TIMER2.0 database was utilized to deduce immune infiltration characteristics. "ELMER v.2" was used to reconstruct TF-methylation-gene regulatory network. Immunotherapy and chemotherapy response predictions were implemented by the TIDE algorithm and GDSC database, respectively. In vitro and in vivo experiments were conducted to verify the results and clarify the regulatory mechanism of lncRNA. RESULTS: In glioma, a TGF-ß signaling-related 15-lncRNA signature was constructed, including AC010173.1, HOXA-AS2, AC074286.1, AL592424.1, DRAIC, HOXC13-AS, AC007938.1, AC010729.1, AC013472.3, AC093895.1, AC131097.4, AL606970.4, HOXC-AS1, AGAP2-AS1, and AC002456.1. This signature proved to be a reliable prognostic tool, with high risk indicating an unfavorable prognosis and being linked to malignant clinicopathological and genomic mutation traits. Risk levels were associated with different immune infiltration landscapes, where high risk was indicative of high levels of macrophage infiltration. In addition, high risk also suggested better immunotherapy and chemotherapy response. cg05987823 was an important methylation site in glioma progression, and AP-1 transcription factor family participated in the regulation of signature lncRNA expression. AGAP2-AS1 knockdown in in vitro and in vivo experiments inhibited the proliferation, migration, and invasion of glioma cells, as well as the growth of glioma, by downregulating the expression levels of NF-κB and ERK 1/2 in the TGF-ß signaling pathway. CONCLUSIONS: A prognostic lncRNA signature of TGF-ß signaling was established in glioma, which can be used for prognostic judgment, immune infiltration status inference, and immunotherapy response prediction. AGAP2-AS1 plays an important role in glioma progression.

Identification and Analysis of Glioblastoma Biomarkers Based on Single Cell Sequencing.

Glioblastoma (GBM) is one of the most common and aggressive primary adult brain tumors. Tumor heterogeneity poses a great challenge to the treatment of GBM, which is determined by both heterogeneous GBM cells and a complex tumor microenvironment. Single-cell RNA sequencing (scRNA-seq) enables the transcriptomes of great deal of individual cells to be assayed in an unbiased manner and has been applied in head and neck cancer, breast cancer, blood disease, and so on. In this study, based on the scRNA-seq results of infiltrating neoplastic cells in GBM, computational methods were applied to screen core biomarkers that can distinguish the discrepancy between GBM tumor and pericarcinomatous environment. The gene expression profiles of GBM from 2343 tumor cells and 1246 periphery cells were analyzed by maximum relevance minimum redundancy (mRMR). Upon further analysis of the feature lists yielded by the mRMR method, 31 important genes were extracted that may be essential biomarkers for GBM tumor cells. Besides, an optimal classification model using a support vector machine (SVM) algorithm as the classifier was also built. Our results provided insights of GBM mechanisms and may be useful for GBM diagnosis and therapy.

[Health-based risk assessment in the excavating process of VOCs contaminated site].

The dissipative concentration test of VOCs in the remediation process of a typical contaminated site was operated, and three routes of exposure were set up for health risk assessment in the repair process. Analysis showed that carbon tetrachloride was the single pollutant with highest multi-route cumulative non-carcinogenic index, which was as high as 8.86E + 01, and its contribution rate to the integrated non-carcinogenic effects was 74.45%. Respiratory exposure was the exposure route with highest multi-pollutant hazard index, which was 1.01E + 02, accounting for 84. 87% of the comprehensive risk index, and the index of integrated non-carcinogenic damage was 1.19E + 02. 1,2-dichloroethane was the single pollutant with highest multi-route cumulative carcinogenic index, which was as high as 3.08E-02, and its contribution rate to the integrated carcinogenic effects was 69.53%. Respiratory exposure was the exposure route with highest multi-pollutant hazard index, which was 3.96E -02, accounting for 89.39% of the comprehensive risk index, and the index of integrated carcinogenic damage was 4.43E-02.