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pmid:38993245

Identification and Validation of a Novel Tertiary Lymphoid Structures-Related Prognostic Gene Signature in Hepatocellular Carcinoma.

Yin Liu · Chao Bo Li · Yun Peng Zhai · Shao Kang Zhang · Ding Yang Li · Zhi Qiang Gao · Ruo Peng Liang

World journal of oncology · 2024 doi:10.14740/wjon1893

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Experiment

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Data

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Analysis

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pmid:38993245
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2026-11-01T20:29:03Z
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title
Identification and Validation of a Novel Tertiary Lymphoid Structures-Related Prognostic Gene Signature in Hepatocellular Carcinoma.
doi
10.14740/wjon1893
pmid
38993245
authors array · 7 items
[0]
Yin Liu
[1]
Chao Bo Li
[2]
Yun Peng Zhai
[3]
Shao Kang Zhang
[4]
Ding Yang Li
[5]
Zhi Qiang Gao
[6]
Ruo Peng Liang
journal
World journal of oncology
year
2024
abstract
Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors originating from the digestive system. Tertiary lymphoid structures (TLS), non-lymphoid tissues outside of the lymphoid organs, are closely connected to chronic inflammation and tumorigenesis. However, the detailed relationship between TLS and HCC prognosis remained unclear. In this study, we aimed to construct a TLS-related gene signature for predicting the prognosis of HCC patients. Methods: The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated. Results: Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients. Conclusion: In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.
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Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort.
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sections[0] "Abstract" paragraph 2
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Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort.
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The datasets analyzed during the current study are available in the TCGA (https://portal.gdc.cancer.gov/projects, TCGA-LIHC Project) and GEO repository (https://www.ncbi.nlm.nih.gov/geo/, accession number GSE14520, 104580, 109211) and ICGC portal (https://icgc.org/).
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sections[30] "Data Availability" paragraph 2
quote
The datasets analyzed during the current study are available in the TCGA (https://portal.gdc.cancer.gov/projects, TCGA-LIHC Project) and GEO repository (https://www.ncbi.nlm.nih.gov/geo/, accession number GSE14520, 104580, 109211) and ICGC portal (https://icgc.org/).
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A six-gene TLS prognostic model achieved time-dependent overall-survival prediction AUCs of 0.751 at 1 year, 0.732 at 3 years, and 0.713 at 5 years in the TCGA cohort.
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qualitative
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sections[16] "Construction of prognostic model of TLS-related genes in HCC" paragraph 2
quote
The prognostic prediction of OS was also revealed by time-dependent ROC analysis to be 0.751 at 1 year, 0.732 at 3 years, and 0.713 at 5 years (Fig. 5d).
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A six-gene TLS prognostic model achieved time-dependent overall-survival prediction AUCs of 0.751 at 1 year, 0.732 at 3 years, and 0.713 at 5 years in the TCGA cohort.
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The datasets analyzed during the current study are available in the TCGA (https://portal.gdc.cancer.gov/projects, TCGA-LIHC Project) and GEO repository (https://www.ncbi.nlm.nih.gov/geo/, accession number GSE14520, 104580, 109211) and ICGC portal (https://icgc.org/).
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488
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null
platform
3921;571
taxon
Homo sapiens
title
Gene expression data of human hepatocellular carcinoma (HCC)
resolution_checked_at
2026-11-01T15:39:54Z
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licence_read
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Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort.
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cox_ph
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availability_state
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basis
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The datasets analyzed during the current study are available in the TCGA (https://portal.gdc.cancer.gov/projects, TCGA-LIHC Project) and GEO repository (https://www.ncbi.nlm.nih.gov/geo/, accession number GSE14520, 104580, 109211) and ICGC portal (https://icgc.org/).
basis
The paper names GSE14520 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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minimax
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Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38993245", "kind": "science-record", "revision": 3, "content_hash": "sha256:e333cb4af6653dba969f43cbc96f6ef3d302b2939feb9bc05e1f1d242d9867d4", "created_at": "2026-11-01T20:29:03Z", "updated_at": "2026-11-01T22:12:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of a Novel Tertiary Lymphoid Structures-Related Prognostic Gene Signature in Hepatocellular Carcinoma.", "doi": "10.14740/wjon1893", "pmid": "38993245", "authors": ["Yin Liu", "Chao Bo Li", "Yun Peng Zhai", "Shao Kang Zhang", "Ding Yang Li", "Zhi Qiang Gao", "Ruo Peng Liang"], "journal": "World journal of oncology", "year": 2024, "abstract": "Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors originating from the digestive system. Tertiary lymphoid structures (TLS), non-lymphoid tissues outside of the lymphoid organs, are closely connected to chronic inflammation and tumorigenesis. However, the detailed relationship between TLS and HCC prognosis remained unclear. In this study, we aimed to construct a TLS-related gene signature for predicting the prognosis of HCC patients.\nMethods: The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated.\nResults: Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients.\nConclusion: In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.", "claims": [{"id": "claim-method", "statement": "Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38993245", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed during the current study are available in the TCGA (https://portal.gdc.cancer.gov/projects, TCGA-LIHC Project) and GEO repository (https://www.ncbi.nlm.nih.gov/geo/, accession number GSE14520, 104580, 109211) and ICGC portal (https://icgc.org/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38993245", "locator": "sections[30] \"Data Availability\" paragraph 2", "quote": "The datasets analyzed during the current study are available in the TCGA (https://portal.gdc.cancer.gov/projects, TCGA-LIHC Project) and GEO repository (https://www.ncbi.nlm.nih.gov/geo/, accession number GSE14520, 104580, 109211) and ICGC portal (https://icgc.org/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A six-gene TLS prognostic model achieved time-dependent overall-survival prediction AUCs of 0.751 at 1 year, 0.732 at 3 years, and 0.713 at 5 years in the TCGA cohort.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38993245", "locator": "sections[16] \"Construction of prognostic model of TLS-related genes in HCC\" paragraph 2", "quote": "The prognostic prediction of OS was also revealed by time-dependent ROC analysis to be 0.751 at 1 year, 0.732 at 3 years, and 0.713 at 5 years (Fig. 5d)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A six-gene TLS prognostic model achieved time-dependent overall-survival prediction AUCs of 0.751 at 1 year, 0.732 at 3 years, and 0.713 at 5 years in the TCGA cohort.", "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:38993245"], "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:GSE14520"], "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:GSE14520"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38993245", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.14740/wjon1893", "sha256": 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