Integrative Analysis Reveals Differential Characteristics of DDR1 Mutant and Wild-type Gastric Cancers and Constructs their Prediction Models

Yonggang Tian; Yunqian Xie; Guirong Yi; FuBing Yu; Feihu Bai; Jun Wang; Dekui Zhang

doi:10.2174/0109298673319260241014054643

Integrative Analysis Reveals Differential Characteristics of DDR1 Mutant and Wild-type Gastric Cancers and Constructs their Prediction Models

Curr Med Chem. 2024 Oct 17. doi: 10.2174/0109298673319260241014054643. Online ahead of print.

Authors

Yonggang Tian¹, Yunqian Xie², Guirong Yi¹, FuBing Yu³, Feihu Bai², Jun Wang⁴, Dekui Zhang¹

Affiliations

¹ Department of Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu Province, China.
² The Gastroenterology Clinical Medical Center of Hainan Province, Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, China.
³ Department of Gastroenterology, Yunnan University Hospital, Kunming City, Yunnan Province, China.
⁴ Department of Gastroenterology, 986 Hospital, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi Province, China.

PMID: 39421995
DOI: 10.2174/0109298673319260241014054643

Abstract

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.

Keywords: DDR1; Gastric cancer; ferroptosis; gene mutation; immune checkpoint; immune score; prognostic model.; tumor stemness.