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.

Chronic kidney disease as a predictive factor for poor prognosis in traumatic brain injury among older adults: a case-control study.

Objective: Traumatic brain injury (TBI) is a highly prevalent neurological disorder that affects a gradually increasing proportion of older adults. Chronic kidney disease (CKD) significantly contributes to global years of life lost, with an estimated one-tenth of the global population affected by CKD. However, it remains unclear whether CKD impacts TBI prognosis. We conducted a case-control study to investigate the clinical outcomes of TBI patients with or without CKD comorbidity and identified the risk factors associated with a poor prognosis. Methods: From January 2017 through April 2023, 11 patients with TBI and CKD were included, and 27 control TBI cases with normal kidney function were matched by age, gender, and admission Glasgow Coma Scale (GCS) score as the control group. Results: The CKD TBI group had a significantly lower GCS score upon discharge (7.1 ± 5.9) compared to the non-CKD TBI group (13.1 ± 2.6) (p < 0.01). ICU stay time and hospitalization expenses were higher in the CKD group than the non-CKD group, though there were no statistical differences. Additionally, patients in the CKD TBI group had a higher frequency of hospital-acquired infections (54.4%) compared with those in the non-CKD TBI group (7.4%) (p < 0.01). The two groups exhibited no differences in hemoglobin levels, albumin levels, or coagulation function. Logistic regression analysis showed that advanced age, low admission GCS score, elevated blood urea, and creatinine levels were associated with a poor neurological prognosis. Conclusion: TBI patients comorbid with CKD have a poorer prognosis than those with normal kidney function.

Tumor buster - where will the CAR-T cell therapy 'missile' go?

Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies' clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.

HOXA5: A crucial transcriptional factor in cancer and a potential therapeutic target.

HOX genes occupy a significant role in embryogenesis, hematopoiesis, and oncogenesis. HOXA5, a member of the A cluster of HOX genes, is essential for establishing the skeleton and normal organogenesis. As previously reported, aberrant HOXA5 expression contributes to anomalies and dysfunction of various organs, as well as affecting proliferation, differentiation, invasion, apoptosis, and other biological processes of tumor cells. Different cancers showed both downregulated and upregulated HOXA5 expression. The most common strategy for controlling HOXA5 downregulated expression may be CpG island hypermethylation. Additionally, current research demonstrated the regulatory network of HOXA5 and its connection with cancer stem cell progression and the immune microenvironment. Epigenetic modulators and upstream regulators, such as DNMTi and retinoic acid, may be beneficial for anti-tumor effects targeting HOXA5. Here, we summarize current knowledge about the HOXA5 gene, its role in various cancers, and its potential therapeutic value.