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pmid:38025816
SLC22A3 that encodes organic cation transporter-3 is associated with prognosis and immunogenicity of human lung squamous cell carcinoma.
Thuy-An Nguyen · Minh-Khang Le · Phuc-Tan Nguyen · Nguyen Quoc Vuong Tran · Tetsuo Kondo · Atsuhito Nakao
Translational lung cancer research · 2023 doi:10.21037/tlcr-23-334
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Experiment
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Complete file
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However, its role in lung squamous cell carcinoma (LSCC) has not been addressed elsewhere.\nMethods: We analyzed gene expression, DNA methylation, and clinicopathological data from The Cancer Genome Atlas - Lung Squamous Cell Carcinoma (TCGA-LUSC) (n=501), a publicly available database exclusively consisting of LSCC patients. Using a 5 FPKM (fragments per kilobase of exon per million mapped fragments) cut-off, we divided LSCC patients into two groups: patients with tumors possessing high and low SLC22A3 expression (SLC22A3-high and SLC22A3-low, respectively). Prognostic significance was determined through Cox analyses and Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS). Differential methylation position (DMP), differentially gene expression, and pathway analyses were performed. Validation was carried out in GSE74777 (n=107), GSE37745 (n=66), GSE162520 (n=45) and GSE161537 (n=17).\nResults: SLC22A3-high LSCC patients had lower OS and DFS rates than SLC22A3-low LSCC patients. The different expression levels of SLC22A3 in LSCC were correlated with the methylation status of the SLC22A3 gene. Pathway analysis indicated that SLC22A3 expression levels were positively correlated with immune-related pathways such as inflammatory response and abundance of infiltrating immune cells in the tumor microenvironment (TME). Notably, in the SLC22A3-high group, many genes encoding immunological checkpoint inhibitory molecules were upregulated. In addition, SLC22A3 expression positively correlated with the Hot Oral Tumor (HOT) score, indicating high tumor immunogenicity.\nConclusions: These findings suggest that high expression of SLC22A3 is associated with poor prognosis and high immunogenicity in LSCC tumors.", "claims": [{"id": "claim-method", "statement": "To assess the prognosis effect of SLC22A3, we employed both non-parametric and parametric analyses, including univariate and multivariate Cox analyses of OS and the Kaplan-Meier curves of OS and DFS rates.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38025816", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "To assess the prognosis effect of SLC22A3, we employed both non-parametric and parametric analyses, including univariate and multivariate Cox analyses of OS and the Kaplan-Meier curves of OS and DFS rates."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We accessed the TCGA-LUSC and retrieved data about gene expression, DNA methylation, and clinicopathological characteristics.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38025816", "locator": "sections[4] \"Data processing\" paragraph 2", "quote": "We accessed the TCGA-LUSC and retrieved data about gene expression, DNA methylation, and clinicopathological characteristics."}], "state": "complete"}, {"id": "claim-target-result", "statement": "These findings suggest that high expression of SLC22A3 is associated with poor prognosis and high immunogenicity in LSCC tumors.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38025816", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "These findings suggest that high expression of SLC22A3 is associated with poor prognosis and high immunogenicity in LSCC tumors."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "These findings suggest that high expression of SLC22A3 is associated with poor prognosis and high immunogenicity in LSCC tumors.", "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:38025816"], "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:GSE161537"], "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:GSE161537"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38025816", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/tlcr-23-334", "sha256": 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