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pmid:36592213
Identification and validation of a PD-L1-related signature from mass spectrometry in gastric cancer.
Xiancong Chen · Deli Mao · Dongsheng Li · Wenchao Li · Hongfa Wei · Cuncan Deng · Hengxing Chen · Changhua Zhang
Journal of cancer research and clinical oncology · 2023 doi:10.1007/s00432-022-04529-6
Paper
complete
Experiment
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Data
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Analysis
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Execution
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Complete file
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According to certain studies, regardless of PD-L1 expression, immunotherapy could be advantageous for individuals with gastric cancer. Therefore, new scoring systems or biomarkers are required to enhance treatment strategies.\nMETHODS: Mass spectrometry and machine learning were used to search for strongly related PD-L1 genes, and the NMF approach was then used to separate gastric cancer patients into two categories. Differentially expressed genes (DEGs) between the two subtypes identified in this investigation were utilized to develop the UBscore predictive model, which was verified by the Gene Expression Omnibus (GEO) database. Coimmunoprecipitation, protein expression, and natural killing (NK) cell coculture experiments were conducted to validate the findings.\nRESULTS: A total of 123 proteins were identified as PD-L1 interactors that are substantially enriched in the proteasome complex at the mRNA level. Using random forest, 30 UPS genes were discovered in the GSE66229 cohort, and ANAPC7 was experimentally verified as one of 123 PD-L1 interactors. Depending on the expression of PD-L1 and ANAPC7, patients were separated into two subgroups with vastly distinct immune infiltration. Low UBscore was related to increased tumor mutation burden (TMB) and microsatellite instability-high (MSI-H). In addition, chemotherapy medications were more effective in individuals with a low UBscore. Finally, we discovered that ANAPC7 might lead to the incidence of immunological escape when cocultured with NK-92 cells.\nCONCLUSION: According to our analysis of the PD-L1-related signature in GC, the UBscore played a crucial role in prognosis and had a strong relationship with TMB, MSI, and chemotherapeutic drug sensitivity. 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METHODS: Mass spectrometry and machine learning were used to search for"], "order_basis": "paper_text_order:19", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Cox regression analyses, both univariate and multivariate, indicated that the UBscore was an independent predictive factor (Fig. 6A, B)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}