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pmid:35928615
The role of miR-145-5p in esophageal squamous cell carcinoma tumor-associated macrophages and selection of immunochemotherapy.
Junhong Lin · Sikai Wu · Kanghao Zhu · Jian Zhang · Xiaoshun Shi · Jianfei Shen · Jianfeng Xu
Journal of thoracic disease · 2022 doi:10.21037/jtd-22-294
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Experiment
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Analysis
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Complete file
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The differences in mRNA levels in cancer tissues and noncancerous tissues were analyzed, and we subsequently investigated the association between miR-145-5p expression and the key parameters of ESCC progression and prognosis. Additionally, cytological experiments were performed to evaluate the biological functions of miR-145-5p. Pathways potentially affected by miR-145-5p were analyzed by Gene Set Enrichment Analysis (GSEA) and REACTOME. We also analyzed the function of miR-145-5p in immune infiltration through the TIMER2 (Tumor Immune Estimation Resource) database.\nResults: The analysis of gene chip data from the TCGA database and GEO database (including GSE13937 and GSE43732) showed that the expression of miR-145-5p is downregulated in ESCC (P<0.05) and that patients with high miR-145-5p levels had lower survival rates (P<0.05). The expression of miR-145-5p was significantly correlated with the disease-free survival (DFS) rate (P<0.05) and M stage (P<0.05) in the TCGA database and was significantly correlated with the T stage (P<0.05) and TNM stage (P<0.05) in the GSE13937 database. Functional experiments showed that miR-145-5p attenuated proliferation (P<0.05), migration (P<0.01) and invasion (P<0.01) in the Eca109 cell line. Both GSEA gene enrichment and REACTOME gene enrichment revealed that miR-145-5p was associated with tumor signaling pathways and immune signaling pathways. Immune infiltration analysis revealed that the expression level of miR-145-5p was significantly correlated with the infiltration level of macrophages (P<0.05) and was positively correlated with the level of gene markers of M2 macrophages and tumor-associated macrophages (P<0.05).\nConclusions: MiR-145-5p acts as a tumor suppressor microRNA in ESCC and is an important noncoding RNA in the high M2-like tumor-associated macrophage infiltration of ESCC. Assessing the miR-145-5p level in ESCC samples has translational meaning, which help illustrate the immune infiltration status, predict the prognostic outcome, and select the type of immunochemotherapy.", "claims": [{"id": "claim-method", "statement": "The relationship between the miR-145-5p expression level and survival rates was obtained with the Kaplan-Meier survival approach, along with the log-rank (Mantel-Cox) test. Pearson correlation coefficients were used to analyze the correlations between miR-145-5p expression and other gene or immune infiltration levels in ESCC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35928615", "locator": "sections[12] \"Statistical analysis\" paragraph 2", "quote": "The relationship between the miR-145-5p expression level and survival rates was obtained with the Kaplan-Meier survival approach, along with the log-rank (Mantel-Cox) test. Pearson correlation coefficients were used to analyze the correlations between miR-145-5p expression and other gene or immune infiltration levels in ESCC."}], "state": "complete"}, {"id": "claim-data-access", "statement": "HTSeq-FPKM and the Clinical Dataset for ESCC were downloaded from the TCGA database (https://cancergenome.nih.gov/). We retrieved the miR expression data of 95 ESCC tissues and 13 normal tissues, as well as the clinical materials of 95 patients with ESCC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35928615", "locator": "sections[3] \"Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data retrieval\" paragraph 2", "quote": "HTSeq-FPKM and the Clinical Dataset for ESCC were downloaded from the TCGA database (https://cancergenome.nih.gov/). We retrieved the miR expression data of 95 ESCC tissues and 13 normal tissues, as well as the clinical materials of 95 patients with ESCC."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The expression of miR-145-5p is downregulated in ESCC, and patients with high miR-145-5p levels had lower survival rates.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "The analysis of gene chip data from the TCGA database and GEO database (including GSE13937 and GSE43732) showed that the expression of miR-145-5p is downregulated in ESCC (P<0.05) and that patients with high miR-145-5p levels had lower survival rates (P<0.05)."}, "evidence": [{"asset": "source:pmid:35928615", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The analysis of gene chip data from the TCGA database and GEO database (including GSE13937 and GSE43732) showed that the expression of miR-145-5p is downregulated in ESCC (P<0.05) and that patients with high miR-145-5p levels had lower survival rates (P<0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The expression of miR-145-5p is downregulated in ESCC, and patients with high miR-145-5p levels had lower survival rates.", "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:35928615"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE13937"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE13937"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35928615", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/jtd-22-294", "sha256": "sha256:a74359ded9f83e8b76c7b2808007a4750c39a13298dca3b4329924aad3d3d23e", "bytes": 42761, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/jtd-22-294", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9344419", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE13937", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE13937", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE13937", "version": null, "note": "HTSeq-FPKM and the Clinical Dataset for ESCC were downloaded from the TCGA database (https://cancergenome.nih.gov/). 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An increased m"], "order_basis": "paper_text_order:4768", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The relationship between the miR-145-5p expression level and survival rates was obtained with the Kaplan-Meier survival approach, along with the log-rank (Mantel-Cox) test. Pearson correlation coefficients were used to analyze the correlations between miR-145-5p expression and other gene or immune infiltration levels in ESCC."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}