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pmid:34772357
Aberrant overexpression of transcription factor Forkhead box D1 predicts poor prognosis and promotes cancer progression in HNSCC.
Jin Li · Tingyuan Yan · Xiang Wu · Xueping Ke · Xin Li · Yumin Zhu · Jianrong Yang · Zhongwu Li
BMC cancer · 2021 doi:10.1186/s12885-021-08868-4
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Complete file
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However, its expression and carcinogenicity in head and neck squamous cell carcinoma (HNSCC) have not been reported yet. This study was to investigate its expression pattern, clinicopathological significance and biological roles in HNSCC.\nMETHODS: HNSCC data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to indicate the detailed expression pattern and outcome association of FOXD1, while Western Blot assay to detect FOXD1 level in a panel of HNSCC cell lines as well as immunocytochemistry to explore FOXD1 protein abundance and sublocation. Series of siRNA-mediated FOXD1 knock-down experiments to assess the proliferation, migration, invasion and anti- apoptosis ability after FOXD1 down-regulation. Bioinformatic analysis to find out which biological function and cancer-related pathways of FOXD1 associated genes involved in.\nRESULTS: FOXD1 mRNA was significantly overexpressed in TCGA-HNSCC, GSE6631, GSE12452, GSE25099 and GSE30784. Besides, IHC results shown that nuclear location FOXD1 protein was significantly higher in primary HNSCC specimens from cohort involved in this study. Also, FOXD1 abundance was significantly correlated with cervical node metastasis and poor over-all/disease-free survival after combination analysis with patient pathological information. siRNA-mediated FOXD1 knock-down significantly inhibited cell proliferation, migration and invasion and induced apoptosis in HNSCC cells. Further analysis of GSEA, GO and KEGG showed that FOXD1 expression was significantly associated with oncological function and cancer-related pathways.\nCONCLUSIONS: Taken together, our study implies that the potential oncogene, FOXD1, facilitates oncological behavior who can be identified as a brand-new HNSCC biomarker with diagnostic and prognostic significance.", "claims": [{"id": "claim-method", "statement": "Normally distributed data were analyzed using an unpaired Student’s t test (two-tailed); multiple comparisons used nonparametric one-way ANOVA. Median cutoff and Log-rank (Mantel-Cox) test was used for survival Kapler-Merier plot.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34772357", "locator": "sections[11] \"Statistical analyses\" paragraph 2", "quote": "Normally distributed data were analyzed using an unpaired Student’s t test (two-tailed); multiple comparisons used nonparametric one-way ANOVA. Median cutoff and Log-rank (Mantel-Cox) test was used for survival Kapler-Merier plot."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The dataset used during the present study is available from the corresponding author upon a reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34772357", "locator": "sections[26] \"notes\" paragraph 1", "quote": "The dataset used during the present study is available from the corresponding author upon a reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Further, as the Kaplan-Meier plots shown, patients with high FOXD1 abundance had obviously shorter overall-survival and disease-free survival than patients with low FOXD1 abundance (Log-rank, P = 0.0014, 0.0025, Figure3 A, B).", "kind": "quantitative", "target": {"value": 0.0014, "unit": "p-value", "tolerance": null, "source": "Further, as the Kaplan-Meier plots shown, patients with high FOXD1 abundance had obviously shorter overall-survival and disease-free survival than patients with low FOXD1 abundance (Log-rank, P = 0.0014, 0.0025, Figure3 A, B)."}, "evidence": [{"asset": "source:pmid:34772357", "locator": "sections[15] \"Aberrant overexpression of FOXD1 in HNSCC patients associated with poor outcome\" paragraph 2", "quote": "Further, as the Kaplan-Meier plots shown, patients with high FOXD1 abundance had obviously shorter overall-survival and disease-free survival than patients with low FOXD1 abundance (Log-rank, P = 0.0014, 0.0025, Figure3 A, B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Further, as the Kaplan-Meier plots shown, patients with high FOXD1 abundance had obviously shorter overall-survival and disease-free survival than patients with low FOXD1 abundance (Log-rank, P = 0.0014, 0.0025, Figure3 A, B).", "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:34772357"], "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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Series of siRNA-mediated FOXD1 knock-down experiments to assess the proliferation, mig", "thological information. siRNA-mediated FOXD1 knock-down significantly inhibited cell proliferation,", "protein abundance and sublocation. Series of siRNA-mediated FOXD1 knock-down experiments to ass", "lysis with patient pathological information. siRNA-mediated FOXD1 knock-down significantly inhi"], "order_basis": "paper_text_order:803", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["proliferation, migration, invasion and anti- apoptosis ability after FOXD1 down-regulation. Bioinfo", "feration, migration and invasion and induced apoptosis in HNSCC cells. Further analysis of GSEA, GO", "(Fig. 6D), KEGG Focal adhesion (Fig. 6E) and Apoptosis (Fig. 6F). In conclusion, combined with cell"], "order_basis": "paper_text_order:906", "id": "assay:3"}, {"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": ["1, GSE12452, GSE25099 and GSE30784. Besides, IHC results shown that nuclear location FOXD1 pr", "s ClusterProfiler [13]. Clinical samples and immunohistochemical staining (IHC) This study protocol was appro", "attern in 110 patients with primary HNSCC by immunohistochemical staining. 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