A High Immune-Related Index with the Suppression of cGAS-STING Pathway is a Key Determinant to Herceptin Resistance in HER2+ Breast Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38993569", "kind": "science-record", "revision": 4, "content_hash": "sha256:357a28bcebc26a1fff2c550ed32946ae7d8f75833fb34143060982dbf0a4429b", "created_at": "2026-11-01T20:29:04Z", "updated_at": "2026-11-01T22:54:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A High Immune-Related Index with the Suppression of cGAS-STING Pathway is a Key Determinant to Herceptin Resistance in HER2+ Breast Cancer.", "doi": "10.7150/ijbs.94868", "pmid": "38993569", "authors": ["Ruizhao Cai", "Qingshan Chen", "Dechang Zhao", "Yan Wang", "Ling Zhou", "Kaiming Zhang", "Jialu Shan", "Zhiling Li", "Yuhong Chen", "Hailiang Zhang", "Gongkan Feng", "Xiaofeng Zhu", "Rong Deng", "Jun Tang"], "journal": "International journal of biological sciences", "year": 2024, "abstract": "Resistance to HER2-targeted therapy is the major cause of treatment failure in patients with HER2+ breast cancer (BC). Given the key role of immune microenvironment in tumor development, there is a lack of an ideal prognostic model that fully accounts for immune infiltration. In this study, WGCNA analysis was performed to discover the relationship between immune-related signaling and prognosis of HER2+ BC. After Herceptin-resistant BC cell lines established, transcriptional profiles of resistant cell line and RNA-sequencing data from GSE76360 cohort were analyzed for candidate genes. 85 samples of HER2+ BC from TCGA database were analyzed by the Cox regression, XGBoost and Lasso algorithm to generalize a credible immune-related prognostic index (IRPI). Correlations between the IRPI signature and tumor microenvironment were further analyzed by multiple algorithms, including single-cell RNA sequencing data analysis. Patients with high IRPI had suppressive tumor immune microenvironment and worse prognosis. The suppression of type I interferon signaling indicated by the IRPI in Herceptin-resistant HER2+ BC was validated. And we elucidated that the suppression of cGAS-STING pathway is the key determinant underlying immune escape in Herceptin-resistant BC with high IRPI. A combination of STING agonist and DS-8201 could serve as a new strategy for Herceptin-resistant HER2+ BC.", "claims": [{"id": "claim-method", "statement": "Univariate Cox regression analysis of OS was performed to identify prognostic genes with p <0.05 using TCGA HER2+ BC cohort. XGBoost algorithm was performed to identify immune-related genes. Finally, the Lasso Cox regression method was used to shrink the candidates to construct the most suitable signature with “glmnet” R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38993569", "locator": "sections[7] \"Construction of the immune-related prognostic index (IRPI)\" paragraph 2", "quote": "Univariate Cox regression analysis of OS was performed to identify prognostic genes with p <0.05 using TCGA HER2+ BC cohort. XGBoost algorithm was performed to identify immune-related genes. Finally, the Lasso Cox regression method was used to shrink the candidates to construct the most suitable signature with “glmnet” R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "RNA expression and corresponding clinical data of HER2+ BC patients enrolled on the 03-311 trial were obtained from GSE76360 cohort.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38993569", "locator": "sections[20] \"Down-regulation of type I IFN signaling is associated with poor prognosis in HER2+ BC patients\" paragraph 2", "quote": "RNA expression and corresponding clinical data of HER2+ BC patients enrolled on the 03-311 trial were obtained from GSE76360 cohort."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The three-gene IRPI showed strong time-dependent prognostic performance in HER2+ breast cancer, with OS AUC values of 0.89, 0.78, and 0.82 at 1, 3, and 5 years and PFS AUC values of 0.81, 0.80, and 0.83 at 1, 3, and 5 years.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38993569", "locator": "sections[21] \"Construction of an immune-related prognostic index (IRPI) for HER2+ BC\" paragraph 4", "quote": "The time-dependent area under ROC curve (AUC) for OS reached 0.89 at 1 year, 0.78 at 3 years, and 0.82 at 5 years, while the time-dependent AUC for PFS reached 0.81 at 1 year, 0.80 at 3 years, and 0.83 at 5 years (Figure 2B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The three-gene IRPI showed strong time-dependent prognostic performance in HER2+ breast cancer, with OS AUC values of 0.89, 0.78, and 0.82 at 1, 3, and 5 years and PFS AUC values of 0.81, 0.80, and 0.83 at 1, 3, and 5 years.", "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:38993569"], "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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