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pmid:35450397
Prediction of Prognosis and Recurrence of Bladder Cancer by ECM-Related Genes.
Hongfan Zhao · Zihao Chen · Yunze Fang · Mingqiang Su · Yipeng Xu · Zhifeng Wang · Michael Adu Gyamfi · Junfeng Zhao
Journal of immunology research · 2022 doi:10.1155/2022/1793005
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Complete file
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This study is aimed at providing models to predict BLCA survival and recurrence by ECM genes.\nMethods: Expression data from BLCA samples in GSE32894, GSE13507, GSE31684, GSE32548, and TCGA-BLCA cohorts were downloaded and analyzed. The ECM-related genes were obtained by differentially expressed gene analysis, stage-associated gene analysis, and random forest variable selection. The ECM was constructed in GSE32894 by the hub ECM-related genes and validated in GSE13507, GSE31684, GSE32548, and TCGA-BLCA cohorts. The correlations of the ECM score with cells (T cells, fibroblasts, etc.) and the response to immunotherapeutic drugs were investigated. Four machine learning models were selected and used to construct models to predict the recurrence of BLCA. A total of 15 paired BLCA and normal tissue specimens, human immortalized uroepithelial cell lines, and bladder cancer cell lines were selected for the validation of the difference in expression of FSTL1 between normal tissues and BLCA.\nResults: Six ECM genes (CTHRC1, MMP11, COL10A1, FSTL1, SULF1, and COL5A3) were recognized to be the hub ECM-related genes. The ECM score of each BLCA patient was calculated using these six selected ECM-related genes. BLCA patients with a high ECM score group had significantly lower overall survival rates than patients in the low ECM score group. We found that the ECM score was positively associated with immune cells and fibroblasts and negatively correlated with tumor purity. When treated with immunotherapy, BLCA patients with a high ECM score presented a high response rate and better prognosis. We also found that the combination of FSTL1, stage, age, and gender achieved an AUC value of 0.76 in predicting bladder cancer recurrence. Based on the RT-qPCR results of FSTL1 gene expression, there was an overall decrease in the mRNA expression of FSTL1 in cancer tissues compared to their adjacent normal tissues. Subsequent in vitro validation demonstrated that the FSTL1 expression was downregulated at the gene and protein level compared to that in SVH cells.\nConclusion: Taken together, our results indicate that ECM-related genes correlate with immune cells, overall survival, and recurrence of BLCA. This study provides a machine learning model for predicting the survival and recurrence of BLCA patients.", "claims": [{"id": "claim-method", "statement": "Using the mRNA expression profiles from GSE32894 and TCGA-BLCA, we determined the genes associated with the tumor stage. In order to select the SAGs, a Pearson correlation analysis was conducted (a p value of 0.05).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35450397", "locator": "sections[4] \"2.2. Identification of Differentially Expressed Genes (DEGs) and Stage-Associated Genes (SAGs)\" paragraph 2", "quote": "Using the mRNA expression profiles from GSE32894 and TCGA-BLCA, we determined the genes associated with the tumor stage. In order to select the SAGs, a Pearson correlation analysis was conducted (a p value of 0.05)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used in this study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35450397", "locator": "sections[24] \"Data Availability\" paragraph 2", "quote": "The datasets used in this study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We also found that the combination of FSTL1, stage, age, and gender achieved an AUC value of 0.76 in predicting bladder cancer recurrence.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35450397", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We also found that the combination of FSTL1, stage, age, and gender achieved an AUC value of 0.76 in predicting bladder cancer recurrence."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We also found that the combination of FSTL1, stage, age, and gender achieved an AUC value of 0.76 in predicting bladder cancer recurrence.", "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:35450397"], "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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Based on the RT-qPCR results of FSTL1 gene expression, there was", "g bladder cancer recurrence. Based on the RT-qPCR results of FSTL1 gene expression, there was"], "order_basis": "paper_text_order:1987", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ll lines (RPMI-1640 medium, Gibco, USA) were cultured in the medium supplemented with 10% fetal bovin"], "order_basis": "paper_text_order:2833", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["and TCGA-BLCA. Table S3: the information of immunohistochemistry (IHC) images from the Human Protein Atlas (H", "of COL5A3, CTHRC1, FSTL1, MMP11, and SULF1. Immunohistochemistry images of COL5A3 in the normal bladder (A) a", "dder (A) and the bladder cancer samples (B). Immunohistochemistry images of CTHRC1 in the normal bladder (C) a", "dder (C) and the bladder cancer samples (D). Immunohistochemistry images of FSTL1 in the normal bladder (E) an"], "order_basis": "paper_text_order:4624", "id": "assay:3"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pearson_r"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Using the mRNA expression profiles from GSE32894 and TCGA-BLCA, we determined the genes associated with the tumor stage. In order to select the SAGs, a Pearson correlation analysis was conducted (a p value of 0.05)."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}