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Updated: Sep 18, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Multidisciplinary analysis of the prognosis and biological function of NUBPL in gastric cancer
Luqian Liu1, Fengyu Zhang2, Jiaye Yu1
1Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.
Background:
Researchers are currently concentrating on molecular markers and potential therapeutic targets associated with gastric cancer in light of recent developments in precision medicine and molecular biology. Disulfidptosis was first proposed in 2023 as a novel programmed cell death mode associated with the cytoskeleton. Disulfidptosis-related proteins are essential for the preservation of protein stability and abnormal expression of disulfidptosis-related genes may be linked to cancer development and drug resistance.
Materials And Method:
The gastric cancer transcriptomic data were retrieved from TCGA database, and disulfidptosis-related genes were identified through literature search. Utilizing machine learning methods such as LASSO, Random Forest (RF), Boruta, SVM-RFE, and XGBoost, the disulfidptosis-related gene NUBPL was determined as a potential predictor for gastric cancer. PPI network was constructed, and the GO database as well as the KEGG database were employed to analyze the protein interactions and pathway enrichment of NUBPL in gastric cancer. Meanwhile, the ESTIMATE algorithm was used for immune infiltration analysis and prediction of immunotherapy response, and the Genomics of Drug Sensitivity in Cancer (GDSC) database was utilized for the drug sensitivity analysis of NUBPL. The role of NUBPL in gastric cancer and its inhibition of disulfidptosis were validated using molecular biological methods.
Results:
The aberrant expression of NUBPL significantly impacts the prognosis of gastric cancer and modulates metabolic and immune-related pathways. In patients with elevated NUBPL expression levels, a reduced number of CD8-positive T cells is associated with adverse prognosis and gastric cancer progression. Elevated NUBPL expression levels can impair the function of chemokines. Moreover, patients with lower NUBPL expression levels exhibit better responses to immunotherapy. We have also identified drugs such as QS11, Imatinib, and AS601245 as potential inhibitors of NUBPL. In vitro experiments have shown that NUBPL affects the invasion and migration of gastric cancer cells, rather than proliferation and apoptosis, by regulating the PPP pathway and inhibiting disulfidptosis.
Conclusion:
This study underscores the pivotal role of NUBPL in gastric cancer progression and highlights its significance as a potential target for targeted therapy and immunotherapy gastric cancer, NUBPL, disulfidptosis, biomarker, immunotherapy, machine learning.
Insights
NUBPL, a novel disulfidptosis-related gene, is identified as a key predictor for gastric cancer prognosis and immunotherapy response. Targeting NUBPL may offer new therapeutic strategies for gastric cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer research is advancing with precision medicine, focusing on molecular markers and therapeutic targets.
- Disulfidptosis, a novel programmed cell death pathway linked to the cytoskeleton, was identified in 2023.
- Disulfidptosis-related genes are crucial for protein stability, and their aberrant expression may influence gastric cancer development and drug resistance.
Purpose of the Study:
- To identify novel molecular markers and therapeutic targets for gastric cancer using machine learning.
- To investigate the role of disulfidptosis-related genes in gastric cancer.
- To evaluate the potential of NUBPL as a prognostic biomarker and therapeutic target in gastric cancer.
Main Methods:
- Gastric cancer transcriptomic data from TCGA were analyzed using multiple machine learning algorithms (LASSO, RF, Boruta, SVM-RFE, XGBoost).
- Literature search identified disulfidptosis-related genes, leading to the selection of NUBPL as a key predictor.
- Bioinformatic analyses included PPI network construction, GO and KEGG pathway enrichment, ESTIMATE for immune infiltration, and GDSC for drug sensitivity.
- Molecular biological methods validated the role of NUBPL and its effect on disulfidptosis.
Main Results:
- NUBPL was identified as a significant predictor of gastric cancer prognosis, impacting metabolic and immune-related pathways.
- Elevated NUBPL expression correlated with reduced CD8-positive T cells, adverse prognosis, and impaired chemokine function.
- Lower NUBPL expression predicted better immunotherapy response, with potential NUBPL inhibitors including QS11, Imatinib, and AS601245.
- In vitro studies showed NUBPL regulates the PPP pathway, inhibits disulfidptosis, and affects gastric cancer cell invasion and migration.
Conclusions:
- NUBPL plays a critical role in gastric cancer progression and serves as a potential biomarker.
- NUBPL represents a promising target for novel targeted therapy and immunotherapy in gastric cancer.
- Understanding NUBPL's role in disulfidptosis offers new avenues for gastric cancer treatment strategies.
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