Diagnostic Value of GDF10 for the Tumorigenesis and Immune Infiltration in Lung Squamous Cell Carcinoma.

OBJECTIVE: Lung squamous cell carcinoma (LUSC) is associated with a low survival rate. Evidence suggests that bone morphogenetic proteins (BMPs) and their receptors (BMPRs) play crucial roles in tumorigenesis and progression. However, a comprehensive analysis of their role in LUSC is lacking. Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC. METHODS: The "R/Limma" package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC, using data from TCGA, GTEx, and GEO databases. Concurrently, the "survminer" packages were employed to investigate their prognostic value and correlation with clinical features in LUSC. The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis (WGCNA). LASSO analysis was conducted to construct a prognostic risk model for LUSC. Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC. Furthermore, based on the tumor immune estimation resource database and tumor-immune system interaction database, the role of the core gene in the tumor microenvironment of LUSC was explored. RESULTS: GDF10 had a significant correlation only with the pathological T stage of LUSC, and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC. A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes (HRASLS, HIST1H2BH, FLRT3, CHEK2, and ALPL) for LUSC. GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression. CONCLUSION: GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.

Identification and validation of DPY30 as a prognostic biomarker and tumor immune microenvironment infiltration characterization in esophageal cancer.

Esophageal cancer (ESCA) is a lethal malignancy and is associated with the alterations of various genes and epigenetic modifications. The protein dpy-30 homolog (DPY30) is a core member of histone H3K4 methylation catalase and its dysfunction is associated with the occurrence and development of cancer. Therefore, the present study investigated the role of DPY30 in ESCA and evaluated the association between the expression of DPY30, the clinicopathological characteristics of ESCA and the tumor immune microenvironment. It conducted a comprehensive analysis of DPY30 in patients with ESCA using The Cancer Genome Atlas (TCGA) database and clinical tissue microarray specimens of ESCA. Immunohistochemistry was performed to assess the expression levels of DPY30 in tissues. Receiver operating curve analysis, Kaplan-Meier survival analysis and Cox regression analysis were performed to identify the diagnostic and prognostic value of DPY30. Gene Set Enrichment Analysis, protein-protein interaction network and Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression data were used to screen DPY30-associated genes and evaluate the immune score of the TCGA samples. The results demonstrated that the expression of mRNA and protein levels of DPY30 were significantly upregulated in tumor tissues compared with normal tissue samples. The expression of DPY30 was closely associated with the poor prognosis of patients with ESCA. The present study also found that DPY30 expression and the pathological characteristics of ESCA were significantly correlated. Additionally, the expression of DPY30 demonstrated a significant positive correlation with various immune cells infiltration. The results suggested that DPY30 might influence tumor immune infiltration. In conclusion, the findings suggested that DPY30 might be a potential prognostic biomarker and an immunotherapeutic target in ESCA.

Inhibition of GABAergic Neurons and Excitation of Glutamatergic Neurons in the Ventrolateral Periaqueductal Gray Participate in Electroacupuncture Analgesia Mediated by Cannabinoid Receptor.

Although electroacupuncture (EA) has become a worldwide practice, little is understood about its precise target in the central nervous system (CNS) and the cell type-specific analgesia mechanism. In the present study, we found that EA has significant antinociceptive effects both in inflammatory and neuropathic pain models. Chemogenetic inhibition of GABAergic neurons in the ventrolateral periaqueductal gray (vlPAG) replicated the effects of EA, whereas the combination of chemogenetic activation of GABAergic neurons and chemogenetic inhibition of glutamatergic neurons in the vlPAG was needed to reverse the effects of EA. Specifically knocking out CB1 receptors on GABAergic neurons in the vlPAG abolished the EA effect on pain hypersensitivity, while specifically knocking out CB1 receptors on glutamatergic neurons attenuated only a small portion of the EA effect. EA synchronously inhibits GABAergic neurons and activates glutamatergic neurons in the vlPAG through CB1 receptors to produce EA-induced analgesia. The CB1 receptors on GABAergic neurons localized in the vlPAG was the basis of the EA effect on pain hypersensitivity. This study provides new experimental evidence that EA can bidirectionally regulate GABAergic neurons and glutamatergic neurons via the CB1 receptors of the vlPAG to produce analgesia effects.