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pmid:38773976
Comprehensive multi-omics analysis of pyroptosis for optimizing neoadjuvant immunotherapy in patients with gastric cancer.
Jia-Bin Wang · You-Xin Gao · Yin-Hua Ye · Qiao-Ling Zheng · Hua-You Luo · Shuan-Hu Wang · Tao Zhang · Qin-Wen Jin · Chao-Hui Zheng · Ping Li · Jian-Xian Lin · Qi-Yue Chen · Long-Long Cao · Ying-Hong Yang · Chang-Ming Huang · Jian-Wei Xie
Theranostics · 2024 doi:10.7150/thno.93124
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Complete file
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However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear. Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis. TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed. The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978). Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS. Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy. Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation. PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC. PRSlow is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center. Importantly, PRSlow marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy. Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment. A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes. The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.", "claims": [{"id": "claim-method", "statement": "Therefore, key differentially expressed genes between the high- and low-pyroptosis groups were screened and then entered into the LASSO-Cox regression to generate prediction models (see “Construction of the PRS” in the Methods section for details).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38773976", "locator": "sections[6] \"Construction of pyroptosis risk score based on pyroptosis phenotype\" paragraph 3", "quote": "Therefore, key differentially expressed genes between the high- and low-pyroptosis groups were screened and then entered into the LASSO-Cox regression to generate prediction models (see “Construction of the PRS” in the Methods section for details)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data generated in this study are publicly available in the Genome Sequence Archive Database (accession numbers: HRA005558). 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The dataset analyzed for this study is available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38773976", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38773976"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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