RESUMO
Gastric cancer (GC) is one of the most common and deadly malignancies in the world. Abnormal activation of hedgehog pathway is closely related to tumor development and progression. However, potential therapeutic targets for GC based on the hedgehog pathway have not been clearly identified. In the present study, we combined single-cell sequencing data and spatial transcriptomics to deeply investigate the role of hedgehog pathway in GC. Based on a comprehensive scoring algorithm, we found that fibroblasts from GC tumor tissues were characterized by a highly enriched hedgehog pathway. By analyzing the development process of fibroblasts, we found that CCND1 plays an important role at the end stage of fibroblast development, which may be related to the formation of tumor-associated fibroblasts. Based on spatial transcriptome data, we deeply mined the role of CCND1 in fibroblasts. We found that CCND1-negative and -positive fibroblasts have distinct characteristics. Based on bulk transcriptome data, we verified that highly infiltrating CCND1 + fibroblasts are a risk factor for GC patients and can influence the immune and chemotherapeutic efficacy of GC patients. Our study provides unique insights into GC and hedgehog pathways and also new directions for cancer treatment strategies.
RESUMO
The Hedgehog pathway is thought to be closely associated with the progression of GC; however, a specific link between the Hedgehog pathway on the prognosis and immune infiltration of gastric cancer is still lacking. This study collected Hedgehog pathway-related genes. The Hedgehog pathway-related pattern were identified by consensus cluster analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to identify the biological functions which were significantly altered between predefined Cluster1 and Cluster2 in consensus clustering. The risk model of gastric cancer based on Hedgehog signaling pathway was constructed by univariate and multivariate COX regression, and the nomogram was constructed. The results showed that there were significant differences in the expression of Hedgehog pathway-related genes between the two groups. In addition, the constructed risk model was significantly correlated with the clinical prognosis and immune cell infiltration level of patients with gastric cancer. The model effectively predicted the efficacy of chemotherapy in GC patients and the sensitivity of drug treatment between groups. We systematically revealed the mechanism of Hedgehog pathway in gastric cancer and selected biomarkers with biological significance from a new perspective, providing potential direction for the treatment of gastric cancer.