Di Chen

Background: Glioblastoma (GBM) was considered the most aggressive type of primary brain tumor, marked by poor clinical outcomes and a high tendency to relapse. The therapeutic efficacy of GBM was significantly compromised by tumor heterogeneity, dysregulated metabolic pathways, the formation of an immunosuppressive microenvironment, and treatment resistance. Therefore, multi-dimensional therapeutic strategies targeting GBM-specific molecular features, its intrinsic properties, and microenvironmental regulatory networks were considered to potentially provide new breakthroughs for overcoming treatment resistance in GBM.Methods: We analyzed single-cell RNA sequencing (scRNA-seq) data processed with the Seurat package to accurately identify cell types. Spatial transcriptomics integrated Multimodal Intersection Analysis, TransferData, and Robust Cell Type Decomposition techniques to characterize the spatial distribution patterns of key cell subtypes. CellChat was employed to assess intercellular communication networks. Furthermore, in vitro experiments confirmed the main regulatory role of YEATS4 (key transcription factor of C2 PCLAF+ subtype) in GBM malignant progression.Results: Through scRNA-seq, we identified the C2 PCLAF+ subtype in GBM and analyzed its molecular characteristics and functional role in tumor progression. This subtype exhibited a unique malignant phenotype, marked by significant proliferative activity, characteristic metabolic reprogramming, and dysregulated cell death regulation mechanisms. Spatial transcriptomics revealed its preferential localization within specific tumor niches. Furthermore, the C2 PCLAF+ subtype established a specific interaction with fibroblasts through the MDK-LRP1 ligand–receptor pair. Critically, silencing YEATS4 in vitro significantly inhibited GBM malignancy. Additionally, the prognostic risk score model based on the C2 PCLAF+ subtype demonstrated significant clinical translational value.Conclusion: Our study systematically elucidated the malignant characteristics of the C2 PCLAF+ subtype and its molecular mechanisms driving GBM progression. This subtype promoted therapeutic resistance through unique metabolic reprogramming, MDK-LRP1-mediated microenvironmental interactions, and immunosuppressive properties. YEATS4 knockdown effectively suppressed malignant tumor behaviors, highlighting its therapeutic potential. These findings provided novel targeted intervention strategies to address GBM heterogeneity and treatment resistance, offering promising avenues for overcoming current therapeutic limitations.

Hepatocellular carcinoma (HCC), a prevalent primary malignant tumor, is notorious for its high mortality rate. Despite advancements in HCC treatment, patient outcomes remain suboptimal. This study endeavors to assess the potential prognostic significance of POLH-AS1 in HCC. In this research, we gathered RNA-Seq information from individuals with HCC in The Cancer Genome Atlas (TCGA). We analyzed the levels of POLH-AS1 expression in both HCC cells and tissues using statistical tests. Additionally, we examined various prognostic factors in HCC using advanced methodologies. Furthermore, we employed Spearman’s rank correlation analysis to examine the association between POLH-AS1 expression and the tumor’s immune microenvironment. Finally, the functional roles of POLH-AS1 in HCC were validated in two HCC cell lines (HEP3B and HEPG2). Our analysis revealed elevated POLH-AS1 expression across various cancers, including HCC, with heightened expression correlating with HCC progression. Notably, POLH-AS1 expression emerged as a potential biomarker for HCC patient survival and prognosis. Mechanistically, we identified the involvement of POLH-AS1 in tumorigenesis pathways such as herpes simplex virus 1 infection, interactions with neuroactive receptors, and the cAMP signaling pathway. Lastly, inhibition of POLH-AS1 was discovered to hinder the proliferation, invasion and migration of HEP3B and HEPG2 HCC cells. POLH-AS1 emerges as a promising prognostic biomarker and therapeutic target for HCC, offering potential avenues for enhanced patient management and treatment strategies.

Background: Hepatocellular carcinoma (HCC) stands as a prevalent malignancy globally, characterized by significant morbidity and mortality. Despite continuous advancements in the treatment of HCC, the prognosis of patients with this cancer remains unsatisfactory. This study aims at constructing a disulfidoptosis‑related long noncoding RNA (lncRNA) signature to probe the prognosis and personalized treatment of patients with HCC. Methods: The data of patients with HCC were extracted from The Cancer Genome Atlas (TCGA) databases. Univariate, multivariate, and least absolute selection operator Cox regression analyses were performed to build a disulfidptosis-related lncRNAs (DRLs) signature. Kaplan–Meier plots were used to evaluate the prognosis of the patients with HCC. Functional enrichment analysis was used to identify key DRLs-associated signaling pathways. Spearman’s rank correlation was used to elucidate the association between the DRLs signature and immune microenvironment. The function of TMCC1-AS1 in HCC was validated in two HCC cell lines (HEP3B and HEPG2). Results: We identified 11 prognostic DRLs from the TCGA dataset, three of which were selected to construct the prognostic signature of DRLs. We found that the survival time of low-risk patients was considerably longer than that of high-risk patients. We further observed that the composition and the function of immune cell subpopulations were significantly different between high- and low-risk groups. Additionally, we identified that sorafenib, 5-Fluorouracil, and doxorubicin displayed better responses in the low-score group than those in the high-score group, based on IC50 values. Finally, we confirmed that inhibition of TMCC1-AS1 impeded the proliferation, migration, and invasion of hepatocellular carcinoma cells. Conclusions: The DRL signatures have been shown to be a reliable prognostic and treatment response indicator in HCC patients. TMCC1-AS1 showed potential as a novel prognostic biomarker and therapeutic target for HCC.

Multiple arachnoid cysts are very rare within the central nervous system. The cysts will sometimes increase in size with age, lead to the mass effect or cerebrospinal fluid (CSF) flow obstruction, and cause some symptoms, which requires the surgery intervention. A 35-year-old female was admitted to our hospital with some symptoms related to hydrocephalus for 1 month. Brain magnetic resonance imaging (MRI) revealed well-marginated cystic lesions with CSF signal intensity in the ventricular and cisternal systems, bilateral temporal lobes, and left occipital lobe. Cine phase-contrast MRI showed the aqueduct of sylvius was blocked by the cyst in the quadrigeminal cistern. We employed endoscopic ventriculocystostomy and septostomy to create the communication of the cyst with ventricular and cistern system. As a result, the patient’s symptoms were relieved. Endoscopic management can be an effective way for treating intracranial multiple arachnoid cysts, which is the first report of this kind. We hope that this report could help improve the management of intracranial arachnoid cysts with the neuroendoscopic technology.