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pmid:36405011
A Lamin Family-Based Signature Predicts Prognosis and Immunotherapy Response in Hepatocellular Carcinoma.
Yongyu Yang · Wang Xiao · Ruoqi Liu · Lei Gao · Junzhang Chen · Heping Kan
Journal of immunology research · 2022 doi:10.1155/2022/4983532
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Our research is aimed at comprehensively estimating the clinical significance of lamin family in hepatocellular carcinoma and constructing a novel lamin family-based signature to predict prognosis and guide the precise immunotherapy.\nMethods: The expression features and prognostic value of LMNA, LMNB1, and LMNB2 were explored in the TCGA and GEO databases. The biological functions of LMNB1 and LMNB2 were validated by in vitro assays. A lamin family-based signature was built using the TCGA training set. The TCGA test set, entire TCGA set, and GSE14520 set were used to validate its predictive power. Univariate and multivariate analyses were performed to evaluate the independence of the lamin family-based signature from other clinicopathological characteristics. A nomogram was constructed using the lamin family-based signature and TNM stage. The associations of this signature with molecular pathways, clinical characteristics, immune cell infiltration, and immunotherapy response were analyzed.\nResults: Lamin family members were upregulated in HCC. Upregulation of LMNB1 and LMNB2 promoted HCC proliferation, migration, and invasion. The predictive signature was initially established based on LMNB1 and LMNB2 which could effectively identify differences in overall survival, immune cell infiltration, and clinicopathological characteristics of high- and low-risk patients. The nomogram showed high prognostic predictive accuracy. Importantly, the lamin family-based signature was correlated with immune suppression and expression of immune checkpoint molecules.\nConclusions: The lamin family-based signature is a robust biomarker to predict overall survival and immunotherapy response in HCC. High-risk score patients have a poorer overall survival and might be more sensitive to immunotherapy. This signature may contribute to improving individualized prognosis prediction and precision immunotherapy for HCC patients.", "claims": [{"id": "claim-method", "statement": "All lamin family members, including LMNA, LMNB1, and LMNB2, were used to conduct univariate Cox regression analyses in the above datasets as well as the GSE14520 set.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36405011", "locator": "sections[5] \"2.3. Evaluation of the Prognostic Significance of Lamin Family Members\" paragraph 2", "quote": "All lamin family members, including LMNA, LMNB1, and LMNB2, were used to conduct univariate Cox regression analyses in the above datasets as well as the GSE14520 set."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The public data included in this study was originated from The Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/) and The Cancer Genome Atlas (https://portal.gdc.cancer. gov/). The experimental data that support the findings of this study are available on request from the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36405011", "locator": "sections[31] \"Data Availability\" paragraph 2", "quote": "The public data included in this study was originated from The Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/) and The Cancer Genome Atlas (https://portal.gdc.cancer. gov/). The experimental data that support the findings of this study are available on request from the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The lamin family-based signature, combined with TNM stage in a nomogram, predicted overall survival in HCC with 1-, 3-, and 5-year AUCs of 0.715, 0.742, and 0.707, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36405011", "locator": "sections[25] \"3.6. Construction and Evaluation of the Nomogram\" paragraph 2", "quote": "The AUCs of the nomogram at 1 year (Figure 8(e)), 3 years (Figure 8(f)), and 5 years (Figure 8(g)) were 0.715, 0.742, and 0.707, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The lamin family-based signature, combined with TNM stage in a nomogram, predicted overall survival in HCC with 1-, 3-, and 5-year AUCs of 0.715, 0.742, and 0.707, respectively.", "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:36405011"], "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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Cell Culture and Plasmid Transfection The normal liver cell line (LO2, GNHu 6) and", "(Guangzhou, China, Uminebio-20211223). Cell transfection was performed using Lipofectamine 2000 reage"], "order_basis": "paper_text_order:2631", "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": ["ademy of Sciences (Shanghai, China) and were cultured in DMEM with 10% fetal bovine serum (FBS). All", "ell lines (Huh7, SCSP-526; MHCC97H, TCHu 94; HepG2, SCSP-510; Hep3B, SCSP-5045) were purchased"], "order_basis": "paper_text_order:2748", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ccording to the manufacturer's instructions. 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