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Introduction: The molecular typing of gastric cancer by TCGA is significant for the precision treatment of gastric cancer. However, the molecular typing of gastric cancer by TCGA lacks the typing of the rare gene DDR1. Therefore, this study aimed to integrate the analysis to reveal the differential features of DDR1 mutant and wild-type gastric cancers and construct their prediction models.
Methods: RNAseq data from 375 gastric cancer patients were downloaded from the TCGA database to comprehensively compare the differences between mutant DDR1 and wild-type DDR1 gastric cancers and construct a prognostic model for wild-type DDR1 gastric cancer.
Results: First, the mutation rate of DDR1 in gastric cancer was 3.23%. Second, the upregulated genes of mutant DDR1 gastric cancer were different from those of wild-type DDR1 gastric cancer in terms of KEGG and GO enrichment. Next, both mutant DDR1 gastric cancers and wild-type DDR1 gastric cancers were associated with EPIC scores and tumour stemness in macrophages. In addition, mutant DDR1 gastric cancers were associated with the iron death-related genes RPL8, CS, and FANCD2 and the m6A-related gene RBM15, compared with wild-type DDR1 gastric cancers. Finally, the established LASSO regression model confirmed that the survival rate of the high-risk group of wild-- type DDR1 gastric cancer would be lower than that of the low-risk group.
Conclusion: This study may provide a new molecular typing method for gastric cancer by comparing the differences between mutant DDR1 and wild-type DDR1 gastric cancer.
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http://dx.doi.org/10.2174/0109298673319260241014054643 | DOI Listing |
J Biomed Res
June 2025
Department of Cancer Biology and Innovation, Guoke Ningbo Life and Health Industry Research Institute, Ningbo, Zhejiang, China.
Gastric cancer (GC) is a prevalent and devastating disease with poor prognosis. Lack of biomarkers for early detection and effective targeted therapeutics for GC patients represent two major challenges for this disease. Through iTRAQ-LC-MS/MS phosphoproteomics analysis of 14 GC gastric epithelial cell lines, we discovered Discoidin Domain Receptor tyrosine kinase 1 ( ) as a top potential drug target out of 40 tyrosine kinases detected along with > 1000 phosphoproteins profiled.
View Article and Find Full Text PDFDiscov Oncol
March 2025
Department of Oncology, College of Clinical Medicine, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, 646000, China.
Discoidin domain receptor 1 (DDR1) has emerged as a promising therapeutic target in oncology due to its unique role in tumor-stroma interactions and its involvement in key signaling pathways that drive cancer progression. DDR1 is homologous to the transmembrane receptor tyrosine kinase (RTK) family and uniquely requires binding to collagen for its activation. It regulates several cellular processes related to tumor cell proliferation, metabolism, migration, stromal remodeling, and epithelial-mesenchymal transition (EMT), ultimately influencing patient survival.
View Article and Find Full Text PDFCurr Med Chem
October 2024
Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China.
Introduction: The molecular typing of gastric cancer by TCGA is significant for the precision treatment of gastric cancer. However, the molecular typing of gastric cancer by TCGA lacks the typing of the rare gene DDR1. Therefore, this study aimed to integrate the analysis to reveal the differential features of DDR1 mutant and wild-type gastric cancers and construct their prediction models.
View Article and Find Full Text PDFAdv Sci (Weinh)
September 2024
Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, Scientific Research Center, The Biobank, The Seventh Affiliated Hospital of Sun Yat-Sen University, No. 628 Zhenyuan Road, Shenzhen, Guangdong, 518107, China.
The extracellular matrix (ECM) has been demonstrated to be dysregulated and crucial for malignant progression in gastric cancer (GC), but the mechanism is not well understood. Here, that discoidin domain receptor 1 (DDR1), a principal ECM receptor, is recognized as a key driver of GC progression is reported. Mechanistically, DDR1 directly interacts with the PAS domain of hypoxia-inducible factor-1α (HIF-1α), suppresses its ubiquitination and subsequently strengthens its transcriptional regulation of angiogenesis.
View Article and Find Full Text PDFExp Cell Res
February 2023
Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, No.628, Zhen yuan Road, Guang ming District, Shenzhen, 518107, China; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong, 51