Development of a Toll-Like Receptor-Based Gene Signature That Can Predict Prognosis, Tumor Microenvironment, and Chemotherapy Response for Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34621787", "kind": "science-record", "revision": 4, "content_hash": "sha256:b1d068a40b3a43a3f252717027183d21a3daa72b338b1afd439c5c3c0ca09162", "created_at": "2026-11-01T17:36:15Z", "updated_at": "2026-11-01T22:04:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development of a Toll-Like Receptor-Based Gene Signature That Can Predict Prognosis, Tumor Microenvironment, and Chemotherapy Response for Hepatocellular Carcinoma.", "doi": "10.3389/fmolb.2021.729789", "pmid": "34621787", "authors": ["Lixia Liu", "Bin Liu", "Jie Yu", "Dongyun Zhang", "Jianhong Shi", "Ping Liang"], "journal": "Frontiers in molecular biosciences", "year": 2021, "abstract": "Objective: Emerging evidence highlights the implications of the toll-like receptor (TLR) signaling pathway in the pathogenesis and therapeutic regimens of hepatocellular carcinoma (HCC). Herein, a prognostic TLR-based gene signature was conducted for HCC. Methods: HCC-specific TLRs were screened in the TCGA cohort. A LASSO model was constructed based on prognosis-related HCC-specific TLRs. The predictive efficacy, sensitivity, and independency of this signature was then evaluated and externally verified in the ICGC, GSE14520, and GSE76427 cohorts. The associations between this signature and tumor microenvironment (stromal/immune score, immune checkpoint expression, and immune cell infiltrations) and chemotherapy response were assessed in HCC specimens. The expression of TLRs in this signature was verified in HCC and normal liver tissues by Western blot. Following si-MAP2K2 transfection, colony formation and apoptosis of Huh7 and HepG2 cells were examined. Results: Herein, we identified 60 HCC-specific TLRs. A TLR-based gene signature (MAP2K2, IRAK1, RAC1, TRAF3, MAP3K7, and SPP1) was conducted for HCC prognosis. High-risk patients exhibited undesirable outcomes. ROC curves confirmed the well prediction performance of this signature. Multivariate Cox regression analysis demonstrated that the signature was an independent prognostic indicator. Also, high-risk HCC was characterized by an increased immune score, immune checkpoint expression, and immune cell infiltration. Meanwhile, high-risk patients displayed higher sensitivity to gemcitabine and cisplatin. The dysregulation of TLRs in the signature was confirmed in HCC. MAP2K2 knockdown weakened colony formation and elevated apoptosis of Huh7 and HepG2 cells. Conclusion: Collectively, this TLR-based gene signature might assist clinicians to select personalized therapy programs for HCC patients.", "claims": [{"id": "claim-method", "statement": "HCC-specific TLRs were utilized for univariate Cox regression analyses of overall survival (OS) in the TCGA cohort. For minimizing the risk of overfitting, TLRs with p < 0.05 were retained for constructing a least absolute shrinkage and selection operator (LASSO) Cox regression model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34621787", "locator": "sections[5] \"Developing and Validating a TLR-Based Gene Signature for HCC Prognosis\" paragraph 2", "quote": "HCC-specific TLRs were utilized for univariate Cox regression analyses of overall survival (OS) in the TCGA cohort. For minimizing the risk of overfitting, TLRs with p < 0.05 were retained for constructing a least absolute shrinkage and selection operator (LASSO) Cox regression model."}], "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 author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34621787", "locator": "sections[31] \"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 author."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34621787"], "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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Following si-MAP2K2 transfection, colony fo"], "order_basis": "paper_text_order:973", "id": "assay:1"}, {"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": ["tissues by Western blot. Following si-MAP2K2 transfection, colony formation and apoptosis of Huh7 and", "n the signature was confirmed in HCC. MAP2K2 knockdown weakened colony formation and elevated apopt", "ormed consent was obtained. Cell Culture and Transfection Huh7 and HepG2 cells were purchased from ATC", "U/mL penicillin, and 100 mg/L streptomycin. Transfection was carried out according to the instruction"], "order_basis": "paper_text_order:1006", "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": 0.93, "evidence": ["si-MAP2K2 transfection, colony formation and apoptosis of Huh7 and HepG2 cells were examined. Resul", "kdown weakened colony formation and elevated apoptosis of Huh7 and HepG2 cells. Conclusion: Collect"], "order_basis": "paper_text_order:1041", "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": 0.99, "evidence": [", colony formation and apoptosis of Huh7 and HepG2 cells were examined. Results: Herein, we ide", "formation and elevated apoptosis of Huh7 and HepG2 cells. Conclusion: Collectively, this TLR-ba", "chased from ATCC (United States), which were cultured in DMEM (ThermoFisher Scientific, United States", "epG2 cells were seeded in a 6-well plate and cultured until the cell confluence was 50–70%; 24 h b"], "order_basis": "paper_text_order:1063", "id": "assay:4"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["HCC-specific TLRs were utilized for univariate Cox regression analyses of overall survival (OS) in the TCGA cohort. For minimizing the risk of overfitting, TLRs with p < 0.05 were retained for constructing a least absolute shrinkage and selection operator (LASSO) Cox regression model."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}