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Association of CAB39L gene methylation in peripheral blood leukocytes with the risk, chemotherapy efficacy and prognosis of gastric cancer and construction of risk prediction model
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DOI：10.21037/tcr-2025-2044.png)
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Abstract
En 中文
Background: Gastric cancer (GC) is a highly prevalent malignant tumor of the digestive tract worldwide, and there is an urgent need to explore non-invasive molecular markers for supporting precise clinical diagnosis and treatment. The study was to explore the correlation between CAB39L gene methylation in peripheral blood leukocytes (PBLs) and the risk, chemotherapy efficacy, and prognosis of GC, and correspondingly construct risk prediction model. Methods: Online databases were used for bioinformatics analysis of CAB39L in GC tissues. A two-phased approach was subsequently employed: in the discovery stage (100 GC patients and 100 controls), we detected the methylation levels of all CpG sites in CAB39L to screen for potential CpG sites/regions associated with GC and response to platinum plus fluorouracil (PPF) treatment, and these findings were further validated in independent samples (250 GC patients and 250 controls). In addition, GC patients were followed up to investigate the correlation between CAB39L gene methylation and prognostic outcomes. Nomogram risk prediction models were constructed by integrating CpG sites, environmental and clinical parameters. The expression levels of CAB39L in the peripheral blood of 34 GC patients were detected by quantitative realtime polymerase chain reaction (qRT-PCR). Finally, the gene-environment interactions were investigated. Results: Utilizing online databases, we discovered a negative association between the mRNA (messenger RNA) expression of CAB39L and the levels of DNA methylation, as well as a positive correlation with the half maximal inhibitory concentration (IC50) values of 5-fluorouracil and cisplatin in GC tissues. In two stages study, it was found that the methylation status of three sites plus two CpG islands (CAB39La2, CAB39Lb3, CAB39Lb14, CAB39L-a, CAB39L-b) were associated with the risk of GC (P-BH<0.05). The methylation status of three sites and one island shore (CAB39La13, CAB39Lc6, CAB39Lc7, CAB39L-c) were found to be related to the efficacy of PPF chemotherapy (P-BH<0.05). The constructed nomogram had a good predictive value for the effect of PPF chemotherapy. The association between CAB39L gene methylation and prognosis of GC was not found in the follow-up study (P>0.05). Compared with the hypomethylation group of GC patients, the mRNA expression level of CAB39L in the hypermethylation group was decreased (P=0.041). Interactions between CAB39L methylation and environmental factors were observed. Conclusions: Our findings suggested that methylation of CAB39L in PBLs was associated with GC risk and chemotherapy response, and the prediction model based on CAB39L methylation site has potential value in predicting the efficacy of chemotherapy. Elevated CAB39L methylation levels of GC patients might influence gene expression. This study provides theoretical support for the diagnosis and treatment of GC patients.
Keywords:
Gastric cancer (GC)
CAB39L
DNA methylation
peripheral blood leukocytes (PBLs)
prediction model
Journal
T
IF:
1.7
Papers:
429
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0