Construction and validation of a novel lysosomal signature for hepatocellular carcinoma prognosis, diagnosis, and therapeutic decision-making.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38114725", "kind": "science-record", "revision": 2, "content_hash": "sha256:c63aa678fbf8bdadde7d57e7fce8e5d3d2b924b2aed49cc72f4bad5bb3a8c480", "created_at": "2026-11-01T19:20:03Z", "updated_at": "2026-11-01T21:32:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction and validation of a novel lysosomal signature for hepatocellular carcinoma prognosis, diagnosis, and therapeutic decision-making.", "doi": "10.1038/s41598-023-49985-3", "pmid": "38114725", "authors": ["Jianlin Chen", "Gan Gao", "Yufang He", "Yi Zhang", "Haixia Wu", "Peng Dai", "Qingzhu Zheng", "Hengbin Huang", "Jiamiao Weng", "Yue Zheng", "Yi Huang"], "journal": "Scientific reports", "year": 2023, "abstract": "Lysosomes is a well-recognized oncogenic driver and chemoresistance across variable cancer types, and has been associated with tumor invasiveness, metastasis, and poor prognosis. However, the significance of lysosomes in hepatocellular carcinoma (HCC) is not well understood. Lysosomes-related genes (LRGs) were downloaded from Genome Enrichment Analysis (GSEA) databases. Lysosome-related risk score (LRRS), including eight LRGs, was constructed via expression difference analysis (DEGs), univariate and LASSO-penalized Cox regression algorithm based on the TCGA cohort, while the ICGC cohort was obtained for signature validation. Based on GSE149614 Single-cell RNA sequencing data, model gene expression and liver tumor niche were further analyzed. Moreover, the functional enrichments, tumor microenvironment (TME), and genomic variation landscape between LRRSlow/LRRShigh subgroup were systematically investigated. A total of 15 Lysosomes-related differentially expressed genes (DELRGs) in HCC were detected, and then 10 prognosis DELRGs were screened out. Finally, the 8 optimal DELRGs (CLN3, GBA, CTSA, BSG, APLN, SORT1, ANXA2, and LAPTM4B) were selected to construct the LRRS prognosis signature of HCC. LRRS was considered as an independent prognostic factor and was associated with advanced clinicopathological features. LRRS also proved to be a potential marker for HCC diagnosis, especially for early-stage HCC. Then, a nomogram integrating the LRRS and clinical parameters was set up displaying great prognostic predictive performance. Moreover, patients with high LRRS showed higher tumor stemness, higher heterogeneity, and higher genomic alteration status than those in the low LRRS group and enriched in metabolism-related pathways, suggesting its underlying role in the progression and development of liver cancer. Meanwhile, the LRRS can affect the proportion of immunosuppressive cell infiltration, making it a vital immunosuppressive factor in the tumor microenvironment. Additionally, HCC patients with low LRRS were more sensitive to immunotherapy, while patients in the high LRRS group responded better to chemotherapy. Upon single-cell RNA sequencing, CLN3, GBA, and LAPTM4B were found to be specially expressed in hepatocytes, where they promoted cell progression. Finally, RT-qPCR and external datasets confirmed the mRNA expression levels of model genes. This study provided a direct links between LRRS signature and clinical characteristics, tumor microenvironment, and clinical drug-response, highlighting the critical role of lysosome in the development and treatment resistance of liver cancer, providing valuable insights into the prognosis prediction and treatment response of HCC, thereby providing valuable insights into prognostic prediction, early diagnosis, and therapeutic response of HCC.", "claims": [{"id": "claim-method", "statement": "To verify the ability of the LRRS accurately and independently predict the prognosis of HCC patients, univariate and multivariate Cox regression analyses was performed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38114725", "locator": "sections[16] \"Stratified analysis, independent prognostic analysis, and diagnostic analysis\" paragraph 3", "quote": "To verify the ability of the LRRS accurately and independently predict the prognosis of HCC patients, univariate and multivariate Cox regression analyses was performed."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from The Cancer Genome Atlas(TCGA, https://portal.gdc.cancer.gov/repository)(search term: TCGA-LIHC), International Cancer Genome Consortium (ICGC) Japanese liver cancer (ICGC-LIRI-JP) cohort (https://dcc.icgc.org/projects/LIRI-JP), HPA (http://www.proteinatlas.org), and from NCBI GEO: GSE144269 and GSE76427, as well as supplementary materials provided in the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38114725", "locator": "sections[33] \"notes\" paragraph 1", "quote": "The datasets used and/or analyzed during the current study are available from The Cancer Genome Atlas(TCGA, https://portal.gdc.cancer.gov/repository)(search term: TCGA-LIHC), International Cancer Genome Consortium (ICGC) Japanese liver cancer (ICGC-LIRI-JP) cohort (https://dcc.icgc.org/projects/LIRI-JP), HPA (http://www.proteinatlas.org), and from NCBI GEO: GSE144269 and GSE76427, as well as supplementary materials provided in the article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The lysosome-related risk score was an independent prognostic factor for overall survival in HCC.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "According to multivariate cox regression analysis, stage (HR = 1.558, 95% CI = 1.258–1.929) and LRRS (HR = 2.876, 95% CI = 1.923–4.301) was independent factors for OS (Fig. 5A)."}, "evidence": [{"asset": "source:pmid:38114725", "locator": "sections[16] \"Stratified analysis, independent prognostic analysis, and diagnostic analysis\" paragraph 3", "quote": "According to multivariate cox regression analysis, stage (HR = 1.558, 95% CI = 1.258–1.929) and LRRS (HR = 2.876, 95% CI = 1.923–4.301) was independent factors for OS (Fig. 5A)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The lysosome-related risk score was an independent prognostic factor for overall survival in HCC.", "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:38114725"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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