Integrative analysis of the ST6GALNAC family identifies GATA2-upregulated ST6GALNAC5 as an adverse prognostic biomarker promoting prostate cancer cell invasion.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37468844", "kind": "science-record", "revision": 3, "content_hash": "sha256:25a70363390fa6fbdac0841a7c410a7e2c508616584b44095f045df74c2d8e65", "created_at": "2026-11-01T19:02:14Z", "updated_at": "2026-11-01T22:09:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrative analysis of the ST6GALNAC family identifies GATA2-upregulated ST6GALNAC5 as an adverse prognostic biomarker promoting prostate cancer cell invasion.", "doi": "10.1186/s12935-023-02983-x", "pmid": "37468844", "authors": ["Meiqian Li", "Zhihui Ma", "Yuqing Zhang", "Hanyi Feng", "Yang Li", "Weicong Sang", "Rujian Zhu", "Ruimin Huang", "Jun Yan"], "journal": "Cancer cell international", "year": 2023, "abstract": "BACKGROUND: ST6GALNAC family members function as sialyltransferases and have been implicated in cancer progression. However, their aberrant expression levels, prognostic values and specific roles in metastatic prostate cancer (PCa) remain largely unclear.\nMETHODS: Two independent public datasets (TCGA-PRAD and GSE21032), containing 648 PCa samples in total, were employed to comprehensively examine the mRNA expression changes of ST6GALNAC family members in PCa, as well as their associations with clinicopathological parameters and prognosis. The dysregulation of ST6GALNAC5 was further validated in a mouse PCa model and human PCa samples from our cohort (n = 64) by immunohistochemistry (IHC). Gene Set Enrichment Analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and drug sensitivity analyses were performed to enrich the biological processes most related to ST6GALNAC5. Sulforhodamine B, transwell, luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to examine the PCa cell proliferation, invasion and transcriptional regulation, respectively.\nRESULTS: Systematical investigation of six ST6GALNAC family members in public datasets revealed that ST6GALNAC5 was the only gene consistently and significantly upregulated in metastatic PCa, and ST6GALNAC5 overexpression was also positively associated with Gleason score and predicted poor prognosis in PCa patients. IHC results showed that (1) ST6GALNAC5 protein expression was increased in prostatic intraepithelial neoplasia and further elevated in PCa from a PbCre;PtenF/F mouse model; (2) overexpressed ST6GALNAC5 protein was confirmed in human PCa samples comparing with benign prostatic hyperplasia samples from our cohort (p < 0.001); (3) ST6GALNAC5 overexpression was significantly correlated with perineural invasion of PCa. Moreover, we first found transcription factor GATA2 positively and directly regulated ST6GALNAC5 expression at transcriptional level. ST6GALNAC5 overexpression could partially reverse GATA2-depletion-induced inhibition of PCa cell invasion. The GATA2-ST6GALNAC5 signature exhibited better prediction on the poor prognosis in PCa patients than GATA2 or ST6GALNAC5 alone.\nCONCLUSIONS: Our results indicated that GATA2-upregulated ST6GALNAC5 might serve as an adverse prognostic biomarker promoting prostate cancer cell invasion.", "claims": [{"id": "claim-method", "statement": "The disease-free survival (DFS) was analyzed using Kaplan–Meier survival analysis with log-rank test in PCa patients. p < 0.05 was regarded as statistical significance. The significance of gene relationship with DFS was defined with hazard ratio (HR) and 95% confidence interval (CI) in Cox Proportional-Hazards model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37468844", "locator": "sections[5] \"Kaplan–Meier survival analysis\" paragraph 2", "quote": "The disease-free survival (DFS) was analyzed using Kaplan–Meier survival analysis with log-rank test in PCa patients. p < 0.05 was regarded as statistical significance. The significance of gene relationship with DFS was defined with hazard ratio (HR) and 95% confidence interval (CI) in Cox Proportional-Hazards model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repositories and accession numbers can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37468844", "locator": "sections[41] \"Availability of data and materials\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repositories and accession numbers can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "GATA2-upregulated ST6GALNAC5 might serve as an adverse prognostic biomarker promoting prostate cancer cell invasion.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37468844", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our results indicated that GATA2-upregulated ST6GALNAC5 might serve as an adverse prognostic biomarker promoting prostate cancer cell invasion."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "GATA2-upregulated ST6GALNAC5 might serve as an adverse prognostic biomarker promoting prostate cancer cell invasion.", "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:37468844"], "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:GSE21032"], "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:GSE21032"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37468844", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-023-02983-x", "sha256": "sha256:0fb84005400f93999d2068f0f2c8009392259a204aff1a6de11e54e746edf9ae", "bytes": 68394, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12935-023-02983-x", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10355028", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE21032", "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=GSE21032", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE21032", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repositories and accession numbers can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. 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genomic profiling of human prostate cancer", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE21032 not downloaded", "asset:data:geo:GSE21032 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The disease-free survival (DFS) was analyzed using Kaplan–Meier survival analysis with log-rank test in PCa patients. p < 0.05 was regarded as statistical significance. 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Gene Set Enrichment Analysis, Gene On", "our cohort (n = 64) by immunohistochemistry (IHC). Gene Set Enrichment Analysis, Gene Ontolog", "nd predicted poor prognosis in PCa patients. IHC results showed that (1) ST6GALNAC5 protein e", "ng tumor tissues, we looked up the available IHC data of ST6GALNAC family members (ST6GALNAC1"], "order_basis": "paper_text_order:787", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ure, lentivirus-based transduction and siRNA transfection Human PCa cell lines (LNCaP, C4-2, 22Rv1, DU", "ALNAC5-IRES-puromycin or empty vector was co-transfected with pVSV-G and Gag-Pol plasmids into 293FT", "GATA2 or negative control siRNA (siNC) were transfected into cells with Lipofectamine RNAiMAX reagen", "l culture, lentivirus-based transduction and siRNA transfection Human PCa cell lines (LNCaP, C4"], "order_basis": "paper_text_order:2542", "id": "assay:3"}, {"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": ["NCaP, C4-2, 22Rv1, PC3, and BPH-1 cells were cultured in RPMI 1640 medium, while DU145, 293 T and 293"], "order_basis": "paper_text_order:2915", "id": "assay:4"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["logrank_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The disease-free survival (DFS) was analyzed using Kaplan–Meier survival analysis with log-rank test in PCa patients. p < 0.05 was regarded as statistical significance. The significance of gene relationship with DFS was defined with hazard ratio (HR) and 95% confidence interval (CI) in Cox Proportional-Hazards model."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}