Author Correction: Inhibiting macrophage-derived lactate transport restores cGAS-STING signalling and enhances antitumour immunity in glioblastoma.
Explore the source record for details and available documents.
Published Erratum↗
Biomedical subjects
Qianghu Wang
Publications and source records attributed to Qianghu Wang.
Development and preliminary validation of plasma cell-free DNA methylation-based diagnostic prediction model for colorectal cancer detection.
BACKGROUND: Colorectal cancer (CRC) is a common malignancy associated with genetic and epigenetic alterations. Several methylation biomarkers have been investigated for non-invasive CRC detection; however, their reported performance varies across clinical settings, and the detection of early-stage or precancerous disease and discrimination from non-malignant colorectal conditions remain challenging. This exploratory study aimed to identify reproducible CRC-associated plasma cell-free DNA (cfDNA) methylation regions and to develop and preliminarily evaluate diagnostic prediction model for distinguishing CRC from healthy controls and benign samples. METHODS: Public CRC tissue methylation datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify reproducible CRC-associated methylation alterations. Plasma cfDNA methylation was profiled using methyl-CpG-binding-domain enrichment followed by paired-end sequencing in patients with CRC, patients with colorectal polyps, and healthy controls. After quality-control filtering, 30 CRC and healthy-control samples were randomly allocated at the participant level in a 7:3 ratio to a development set comprising 10 patients with CRC and 11 healthy controls and a held-out test set comprising 4 patients with CRC and 5 healthy controls. Hypermethylated regions were selected using least absolute shrinkage and selection operator (LASSO) logistic regression. The 12-region model was evaluated in the held-out test set and subsequently applied to 10 colorectal polyp samples without refitting or recalibration. RESULTS: Tissue methylation analysis identified reproducible CRC-associated alterations across independent datasets. In the plasma development set, 707 differentially methylated regions (DMRs) were identified between CRC and healthy-control samples, including 324 hypermethylated and 383 hypomethylated regions. LASSO regression selected a 12-region hypermethylation signature. In the held-out test set, the model achieved an area under the curve (AUC) of 0.85 [95% confidence interval (CI): 0.579-1.000]. At the development-set-derived threshold, sensitivity was 75.0% (3/4), specificity was 60.0% (3/5), and accuracy was 66.7% (6/9). When the original model was applied to colorectal polyp samples, model scores were significantly higher in both CRC and polyp samples than in healthy controls, while CRC samples showed a tendency toward higher scores than polyp samples. CONCLUSIONS: This exploratory study identified a 12-region plasma cfDNA hypermethylation signature associated with CRC and developed a LASSO-based diagnostic prediction model that showed preliminary discrimination between CRC and healthy controls in a small held-out test set. By integrating tissue methylation evidence with plasma cfDNA profiling, this study expands the repertoire of candidate region-level methylation markers for blood-based CRC detection.
Colorectal cancer (CRC)↗
Inhibiting macrophage-derived lactate transport restores cGAS-STING signalling and enhances antitumour immunity in glioblastoma.
Glioblastoma (GBM) is a malignancy with a complex tumour microenvironment (TME) dominated by GBM stem cells (GSCs) and infiltrated by tumour-associated macrophages (TAMs) and exhibits aberrant metabolic pathways. Lactate is a critical glycolytic metabolite that promotes tumour progression; however, the mechanisms of lactate transport and lactylation in the TME of GBM remain elusive. Here we show that lactate is transported from TAMs to GSCs via MCT4-MCT1. TAMs provide lactate to GSCs, promoting GSC proliferation and inducing lactylation of the non-homologous end joining protein KU70 at lysine 317 (K317), which inhibits cGAS-STING signalling and remodels the immunosuppressive TME. Inhibition of lactate transport or targeting the lactylation of KU70, in combination with the immune checkpoint blockade, demonstrates additive therapeutic benefits in immunocompetent xenograft models. This study unveils TAM-derived lactate and lactylation as critical regulators in GSCs to enforce an immunosuppressive microenvironment, opening avenues for developing combinatorial therapy for GBM.
Glioblastoma↗
Prognostic Role of Global DNA Methylation in Renal Cancer Reveals Decitabine Treatment Benefit.
BACKGROUND: Renal cancer presents a significant global health challenge due to its rising incidence and mortality rates. Often undetected in early stages, it complicates diagnosis and treatment. Current therapies face resistance and limited effectiveness, especially in advanced stages. The diverse subtypes of renal cancer highlight the need for new biomarkers and risk assessment tools for targeted treatments. OBJECTIVE: This study aims to assess the prognostic significance of global DNA methylation (GM) levels in renal cancer, identify new biomarkers, and evaluate the therapeutic potential of the DNA methyltransferase inhibitor decitabine. METHODS: Data on RNA sequencing, gene mutations, DNA methylation, and clinical outcomes were collected from TCGA and GEO databases. We calculated global DNA methylation scores (GMS) and categorized patients into high, intermediate, and low GMS groups. Survival analysis and genomic analyses were conducted to explore the relationships between GMS, clinical outcomes, and tumor characteristics. RESULTS: Higher GMS was identified as an independent prognostic factor associated with worse outcomes in renal cancer. Patients with elevated GMS showed increased mutations, copy number variations, and a more aggressive tumor phenotype. Treatment with decitabine was observed to reduce tumor hypermethylation and downregulate cell cycle pathway activity, indicating potential therapeutic benefits. CONCLUSION: Global DNA methylation plays a significant role in renal cancer prognosis. GMS may serve as valuable biomarkers for prognosis and personalized treatment strategies. Decitabine shows potential efficacy for high GMS patients, particularly through its impact on cell cycle regulation, underscoring the importance of personalized approaches in cancer treatment.
Humans↗