a-flow-cytometry-based-method-for-profiling-immune-cells-human-blood

A Flow Cytometry-Based Method for Profiling Immune Cells in Human Blood and Tumors

Flow cytometry enables the simultaneous characterization of multiple immune-cell populations and their phenotypic subsets in clinical specimens. However, ...

Luoyang Central Hospital Affiliated to Zhengzhou University

Henan Province Engineering Research Center for Multi-omics Precise Diagnosis and Treatment of Lung Diseases

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease, which mainly damages patients' exocrine glands. Sensitive early diagnostic indicators and effective treatments for pSS are lacking. Using machine learning methods to find diagnostic markers and effective therapeutic ways for pSS is of great significance. In our study, first, 1643 differentially expressed genes (DEGs; 737 were upregulated and 906 were downregulated) were ultimately screened out and analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes based on the datasets from the Gene Expression Omnibus. Then, support vector machine, least absolute shrinkage and selection operator regression, random forest, and weighted correlation network analysis were used to screen out feature genes from DEGs. Subsequently, the intersection of the feature genes was taken to screen 10 genes as hub genes. Meanwhile, the analysis of the diagnostic efficiency of 10 hub genes showed their good diagnostic value for pSS, which was validated through immunohistochemistry on the paraffin sections of the labial gland. Subsequently, a multi-factor regulatory network and correlation analysis of hub genes were performed, and the results showed that ELAVL1 and IGF1R were positively correlated with each other but both negatively correlated with the other seven hub genes. Moreover, several meaningful results were detected through the immune infiltration landscape. Finally, we used molecular docking to screen potential therapeutic compounds of pSS based on the hub genes. We found that the small molecules DB08006, DB08036, and DB15308 had good docking scores with ELAVL1 and IGF1R simultaneously. Our study might provide effective diagnostic biomarkers and new therapeutic ideas for pSS.

Diagnostic markers and potential therapeutic agents for Sjögren's syndrome screened through multiple machine learning and molecular docking.

Metastasis is a crucial aspect of disease progression leading to death in patients with prostate cancer (PCa). However, its mechanism remains unclear. We aimed to explore the mechanism of lymph node metastasis (LNM) by analyzing the heterogeneity of tumor microenvironment (TME) in PCa using scRNA-seq.

ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer.

Disulfidptosis is a novel type of cell death induced by disulphide stress that depends on the accumulation of cystine disulphide, causing cytotoxicity and triggering cell death. However, the direct prognostic effect and regulatory mechanism of disulfidptosis-related genes in bladder urothelial carcinoma (BLCA) remain unclear.

A novel model based on disulfidptosis-related genes to predict prognosis and therapy of bladder urothelial carcinoma.

Correction: ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer.

The tumor microenvironment (TME) comprises immune-infiltrating cells that are closely linked to tumor development. By screening and analyzing genes associated with tumor-infiltrating M0 cells, we developed a risk model to provide therapeutic and prognostic guidance in clear cell renal cell carcinoma (ccRCC). First, the infiltration abundance of each immune cell type and its correlation with patient prognosis were analyzed. After assessing the potential link between the depth of immune cell infiltration and prognosis, we screened the infiltrating M0 cells to establish a risk model centered on three key genes (TMEN174, LRRC19, and SAA1). The correlation analysis indicated a positive correlation between the risk score and various stages of the tumor immune cycle, including B-cell recruitment. Furthermore, the risk score was positively correlated with CD8 expression and several popular immune checkpoints (ICs) (TIGIT, CTLA4, CD274, LAG3, and PDCD1). Additionally, the high-risk group (HRG) had higher scores for tumor immune dysfunction and exclusion (TIDE) and exclusion than the low-risk group (LRG). Importantly, the risk score was negatively correlated with the immunotherapy-related pathway enrichment scores, and the LRG showed a greater therapeutic benefit than the HRG. Differences in sensitivity to targeted drugs between the HRG and LRG were analyzed. For commonly used targeted drugs in RCC, including axitinib, pazopanib, temsirolimus, and sunitinib, LRG had lower IC50 values, indicating increased sensitivity. Finally, immunohistochemistry results of 66 paraffin-embedded specimens indicated that SAA1 was strongly expressed in the tumor samples and was associated with tumor metastasis, stage, and grade. SAA1 was found to have a significant pro-tumorigenic effect by experimental validation. In summary, these data confirmed that tumor-infiltrating M0 cells play a key role in the prognosis and treatment of patients with ccRCC. This discovery offers new insights and directions for the prognostic prediction and treatment of ccRCC.

Identification of a risk model for prognostic and therapeutic prediction in renal cell carcinoma based on infiltrating M0 cells.

Disulfidptosis, a newly discovered mode of cell death caused by excessive accumulation of intracellular disulfide compounds, is closely associated with tumor development. This study focused on the relationship between disulfidptosis and clear cell renal cell carcinoma (ccRCC). Firstly, the characterizations of disulfidptosis-related genes (DRGs) in ccRCC were showed, which included number variation (CNV), single nucleotide variation (SNV), DNA methylation, mRNA expression and gene mutation. Then, the ccRCC samples were classified into three clusters through unsupervised clustering based on DRGs. Survival and pathway enrichment differences were evaluated among the three clusters. Subsequently, the differentially expressed genes (DEGs) among the three clusters were screened by univariate Cox, LASSO, and multivariate Cox analysis, and five key DEGs were obtained. Based on the five key DEGs, the ccRCC samples were reclassified into two geneclusters and the survival differences and immune cell infiltration between two geneclusters was investigated. In next step, ccRCC samples were divided into two groups according to PCA scores of five key DEGs, namely high PCA score group (HPSG) and low PCA score group (LPSG). On this basis, differences in survival prognosis, immune cell infiltration and correlation with immune checkpoint, as well as differences in sensitivity to targeted drugs were compared between HPSG and LPSG. The expression levels of four immune checkpoints were higher in HPSG than in LPSG, whereas the LPSG was more sensitive to targeted drug therapy than the HPSG. Finally, validation experiments on HDAC4 indicated that HDAC4 could increase the proliferation and colony formation ability of ccRCC cells.

Prognostic and therapeutic model based on disulfidptosis-related genes for patients with clear cell renal cell carcinoma.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and an increased risk of progression to acute myeloid leukemia (AML). Patients with MDS often develop progressive systemic iron overload due to ineffective erythropoiesis, dysregulated hepcidin expression, and repeated blood transfusions. Excess free iron promotes reactive oxygen species generation through the Fenton reaction, resulting in persistent oxidative stress within the bone marrow microenvironment. These abnormalities are closely associated with ineffective hematopoiesis. Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation. In MDS, ferroptosis appears to play a dual role. In lower-risk disease settings characterized by ineffective erythropoiesis and anemia, ferroptosis-related injury in erythroid-lineage cells may exacerbate ineffective erythropoiesis. In contrast, in higher-risk or clonally progressive disease settings, selective induction of ferroptosis in malignant clonal cells may represent a potential therapeutic strategy. However, current ferroptosis-targeting agents still face several limitations, including poor water solubility, low stability , insufficient bone marrow targeting, and possible toxicity to normal tissues. Nanotechnology may offer a promising approach to address these challenges. Nanocarriers can improve bone marrow targeting through surface modification and optimized physicochemical properties, while also enabling controlled drug release and co-delivery of multiple therapeutic agents to enhance efficacy and reduce side effects. This review summarizes the role of ferroptosis in the pathogenesis and treatment of MDS, discusses the major challenges in current ferroptosis-based therapies, and highlights the opportunities and challenges of nanotechnology-mediated ferroptosis regulation as a potential future strategy for precision treatment of MDS.

Article	Year
Diagnostic markers and potential therapeutic agents for Sjögren's syndrome screened through multiple machine learning and molecular docking. Clinical and experimental immunology\| PubMed ID: 36988140	2023
ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer. Experimental hematology & oncology\| PubMed ID: 37221625	2023
A novel model based on disulfidptosis-related genes to predict prognosis and therapy of bladder urothelial carcinoma. Journal of cancer research and clinical oncology\| PubMed ID: 37541976	2023
Correction: ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer. Experimental hematology & oncology\| PubMed ID: 38769580	2024
Identification of a risk model for prognostic and therapeutic prediction in renal cell carcinoma based on infiltrating M0 cells. Scientific reports\| PubMed ID: 38862642	2024
Prognostic and therapeutic model based on disulfidptosis-related genes for patients with clear cell renal cell carcinoma. Heliyon\| PubMed ID: 38882384	2024
The role and therapeutic potential of nanotechnology-mediated ferroptosis regulation in myelodysplastic syndromes. Frontiers in oncology\| PubMed ID: 42459301	2026

Haojie Wang

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