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

IF 3.5 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Current medicinal chemistry Pub Date : 2024-10-17 DOI:10.2174/0109298673319260241014054643

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

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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.

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综合分析揭示 DDR1 突变型和野生型胃癌的不同特征并构建其预测模型

前言TCGA 胃癌分子分型对胃癌的精准治疗意义重大。然而，TCGA 的胃癌分子分型缺乏对罕见基因 DDR1 的分型。因此，本研究旨在整合分析，揭示DDR1突变型和野生型胃癌的不同特征，并构建其预测模型：方法：从TCGA数据库下载375例胃癌患者的RNAseq数据，全面比较突变型DDR1胃癌与野生型DDR1胃癌的差异，并构建野生型DDR1胃癌的预后模型：结果：首先，DDR1在胃癌中的突变率为3.23%。其次，突变型 DDR1 胃癌的上调基因在 KEGG 和 GO 富集方面与野生型 DDR1 胃癌不同。其次，突变型DDR1胃癌和野生型DDR1胃癌都与EPIC评分和巨噬细胞中的肿瘤干细胞有关。此外，与野生型DDR1胃癌相比，突变型DDR1胃癌与铁死亡相关基因RPL8、CS和FANCD2以及m6A相关基因RBM15有关。最后，建立的LASSO回归模型证实，野生型DDR1胃癌高危人群的生存率低于低危人群：本研究通过比较突变型 DDR1 胃癌和野生型 DDR1 胃癌的差异，为胃癌的分子分型提供了一种新的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current medicinal chemistry 医学-生化与分子生物学

CiteScore

8.60

自引率

2.40%

发文量

468

审稿时长

3 months

期刊介绍： Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.