Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37152025", "kind": "science-record", "revision": 3, "content_hash": "sha256:ae477843e7c1681a1860e002e4198b58ac4ef067f6eb4b9f8923ddfd2a36b52b", "created_at": "2026-11-01T19:01:48Z", "updated_at": "2026-11-01T22:09:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer.", "doi": "10.3389/fonc.2023.1179120", "pmid": "37152025", "authors": ["Shaorui Rui", "Dong Wang", "Yong Huang", "Jingyun Xu", "Hailang Zhou", "Hesong Zhang"], "journal": "Frontiers in oncology", "year": 2023, "abstract": "Objective: To explore new biomarkers related to microsatellite instability in order to better predict prognosis and guide medication.\nMethods: The \"limma\" R package was used to identify differentially expressed genes in GSE24514, and then weighted correlation network analysis was used to select key genes. Different cell types in the tumor microenvironment were identified and analyzed by single-cell sequencing, with a Lasso regression model used to screen prognostic variables. Furthermore, the correlation between microsatellite instability and potential prognostic variables was explored, as well as the expression characteristics and clinical characteristics of the prognostic variables in the TCGA, UALCAN, and HPA databases. PCR assay was used to investigate the expression of SLC4A4 in colorectal cancer cell lines. Finally, we further verified the expression of SLC4A4 by immunohistochemistry.\nResults: First, 844 differentially expressed genes in GSE24514 were identified. Subsequently, weighted co-expression network analysis (WGCNA) of GSE24514 obtained all the genes significantly associated with microsatellite instability (MSI), a total of 1452. Analysis of GSE166555 single cell sequencing data set yielded 1564 differentially expressed genes. The gene sets obtained from the above three analysis processes were intersected, and 174 genes were finally obtained. The Lasso regression model revealed two potential prognostic genes, TIMP1 and SLC4A4, of which, there was a stronger correlation between microsatellite instability and SLC4A4. The mRNA and protein expression of SLC4A4 was significantly decreased in tumors, and patients with low SLC4A4 expression had a poor prognosis. In addition, SLC4A4 was specifically expressed in epithelial cells. In the microenvironment of colorectal cancer, malignant cells have a strong interaction with different stromal cells. PCR showed that SLC4A4 was significantly down-regulated in colorectal cancer cell lines Caco-2, HCT116 and HT29 compared with normal control NCM460 cell lines. Immunohistochemistry also showed low expression of SLC4A4 in colorectal cancer.\nConclusion: SLC4A4, as a tumor suppressor gene, is significantly downregulated and positively correlated with microsatellite instability, thus it may be combined with microsatellite instability to guide colorectal cancer treatment.", "claims": [{"id": "claim-method", "statement": "The MSI score for each tumor was obtained from a previous study (22) and integrated with the gene expression data to calculate the Pearson correlation for each tumor.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37152025", "locator": "sections[8] \"The correlation between genes and MSI\" paragraph 2", "quote": "The MSI score for each tumor was obtained from a previous study (22) and integrated with the gene expression data to calculate the Pearson correlation for each tumor."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37152025", "locator": "sections[24] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper identified SLC4A4 as a significantly downregulated, MSI-associated potential prognostic biomarker for colorectal cancer.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37152025", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The Lasso regression model revealed two potential prognostic genes, TIMP1 and SLC4A4, of which, there was a stronger correlation between microsatellite instability and SLC4A4."}, {"asset": "source:pmid:37152025", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The mRNA and protein expression of SLC4A4 was significantly decreased in tumors, and patients with low SLC4A4 expression had a poor prognosis."}, {"asset": "source:pmid:37152025", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "SLC4A4, as a tumor suppressor gene, is significantly downregulated and positively correlated with microsatellite instability, thus it may be combined with microsatellite instability to guide colorectal cancer treatment."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper identified SLC4A4 as a significantly downregulated, MSI-associated potential prognostic biomarker for colorectal cancer.", "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:37152025"], "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:GSE166555"], "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:GSE166555"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37152025", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2023.1179120", "sha256": "sha256:54eea258f0baca251b380bf7460838b05ee3bc6747b926adb0e8459c2558fa50", "bytes": 36998, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2023.1179120", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10154614", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE166555", "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=GSE166555", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE166555", "version": null, "note": "The original contributions presented in the study are included in the article/supplementary material. 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Results: First, 844 differentially expresse", "pared with normal control NCM460 cell lines. Immunohistochemistry also showed low expression of SLC4A4 in colo"], "order_basis": "paper_text_order:942", "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": 0.99, "evidence": ["he normal colon cell line NCM460. There were cultured in DMEM (HyClone, USA) supplemented with 10% FB", "midified environment at 37°C. The cells were passaged every 2–3 days using 0.25% trypsin (Hyclone)"], "order_basis": "paper_text_order:2630", "id": "assay:2"}, {"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": ["The MSI score for each tumor was obtained from a previous study (22) and integrated with the gene expression data to calculate the Pearson correlation for each tumor."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}