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. 2023 Oct 17;24(20):15259.
doi: 10.3390/ijms242015259.

Exploring the Prognosis-Related Genetic Variation in Gastric Cancer Based on mGWAS

Yuling Zhang  1   2 , Yanping Lyu  1   2 , Liangping Chen  1   2 , Kang Cao  1   2 , Jingwen Chen  1   2 , Chenzhou He  1   2 , Xuejie Lyu  1   2 , Yu Jiang  1   2 , Jianjun Xiang  1   2 , Baoying Liu  1   2 , Chuancheng Wu  1   2
Affiliations

Exploring the Prognosis-Related Genetic Variation in Gastric Cancer Based on mGWAS

Yuling Zhang et al. Int J Mol Sci. .

Abstract

The use of metabolome genome-wide association studies (mGWAS) has been shown to be effective in identifying functional genes in complex diseases. While mGWAS has been applied to biomedical and pharmaceutical studies, its potential in predicting gastric cancer prognosis has yet to be explored. This study aims to address this gap and provide insights into the genetic basis of GC survival, as well as identify vital regulatory pathways in GC cell progression. Genome-wide association analysis of plasma metabolites related to gastric cancer prognosis was performed based on the Generalized Linear Model (GLM). We used a log-rank test, LASSO regression, multivariate Cox regression, GO enrichment analysis, and the Cytoscape software to visualize the complex regulatory network of genes and metabolites and explored in-depth genetic variation in gastric cancer prognosis based on mGWAS. We found 32 genetic variation loci significantly associated with GC survival-related metabolites, corresponding to seven genes, VENTX, PCDH 7, JAKMIP1, MIR202HG, MIR378D1, LINC02472, and LINC02310. Furthermore, this study identified 722 Single nucleotide polymorphism (SNP) sites, suggesting an association with GC prognosis-related metabolites, corresponding to 206 genes. These 206 possible functional genes for gastric cancer prognosis were mainly involved in cellular signaling molecules related to cellular components, which are mainly involved in the growth and development of the body and neurological regulatory functions related to the body. The expression of 23 of these genes was shown to be associated with survival outcome in gastric cancer patients in The Cancer Genome Atlas (TCGA) database. Based on the genome-wide association analysis of prognosis-related metabolites in gastric cancer, we suggest that gastric cancer survival-related genes may influence the proliferation and infiltration of gastric cancer cells, which provides a new idea to resolve the complex regulatory network of gastric cancer prognosis.

Keywords: gastric cancer; metabolome genome-wide association studies; plasma metabolites; prognosis.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
QQ and Manhattan plot of the results of genome-wide association analysis of plasma metabolites associated with gastric cancer prognosis.
Figure 2
Figure 2
Histogram of GO enrichment results of plasma metabolite-related genes associated with gastric cancer prognosis.
Figure 3
Figure 3
Bubble plot of GO enrichment results of plasma metabolite-related genes associated with gastric cancer prognosis.
Figure 4
Figure 4
Survival curve of functional genes of plasma metabolite localization associated with gastric cancer prognosis. The unit of time is month.
Figure 5
Figure 5
Metabolite-gene interaction network diagram. A: Arachidonic acid; B: Guanosine diphosphate mannose; C: P1,P4-Bis (5′-uridyl) tetraphosphate; D: 5′-Methylthioadenosine; E: Cer (d18:0/12:0); F: D-(+)-Tryptophan; G: Uridine diphosphategalactose; H: Paraxanthine; I: Uric acid; J: Palmitoyl sphingomyelin (SM(d18:1/16:0)); K: Indole-3-lactic acid; L: Ornithine; M: Porphobilinogen; N: Dipalmitoylphosphatidylcholine; O: AICAR; P: Methylacetoacetic acid; Q: DL-Dipalmitoylphosphatidylcholine; R: LBF; S: Linoleic acid; T: Phosphoribosyl-ATP; U: Phenylacetylglutamine; V: Glycoursodeoxycholic acid; W: Inosine triphosphate.
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