Prognosis and therapeutic benefits prediction based on NK cell marker genes through single-cell RNA-seq with integrated bulk RNA-seq analysis for hepatocellular carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37554171", "kind": "science-record", "revision": 3, "content_hash": "sha256:2d776f3558d35ca4d4f01c27aec44460f822f6d34750497ce25a83f84f104a3d", "created_at": "2026-11-01T19:02:20Z", "updated_at": "2026-11-01T22:10:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognosis and therapeutic benefits prediction based on NK cell marker genes through single-cell RNA-seq with integrated bulk RNA-seq analysis for hepatocellular carcinoma.", "doi": "10.3389/fonc.2023.1208165", "pmid": "37554171", "authors": ["Yao Yang", "Shaopin She", "Liying Ren", "Bigeng Zhao", "Dongbo Chen", "Hongsong Chen"], "journal": "Frontiers in oncology", "year": 2023, "abstract": "Tumor-infiltrating immune cells greatly participate in regulating tumorigenesis and metastasis of hepatocellular carcinoma (HCC). Natural killer cell, as an important role of innate immunity, plays an indispensable role in antitumor immunity and regulate tumor development. In this study, we firstly identified 251 NK cell marker genes of HCC based on single-cell RNA sequencing data. Subsequently, an NK cell marker genes-related prognostic signature (NKPS) was developed in the cancer genome atlas (TCGA) cohort for risk stratification and prognosis prediction. The predictive value of the NKPS in prognosis was well validated in different clinical subgroups and three external datasets (ICGC-LIHC cohort, GSE14520 cohort and Guilin cohort). Moreover, multivariate analysis revealed the independent prognostic value of NKPS for OS in HCC. Further functional analysis indicated the NKPS was associated with basic cellular processes, that may contribute to the development and progression of HCC. Thereafter, immune characteristics as well as the therapeutic benefits in NKPS risk score-defined subgroups were analyzed. Patients with low-risk score exhibited immune-active status, manifested as higher immune scores, more infiltration of CD8+ T cells and macrophage M1, and higher T-cell receptor (TCR) richness and diversity. Remarkably, the NKPS was negatively correlated with immunotherapy response-related signatures. In addition, the low-risk group exhibited significantly improved therapeutic benefits, either from immunotherapy or traditional chemotherapy and target therapy. Overall, the NKPS showed an excellent predictive value for prognosis and therapeutic responses for HCC, which might also provide novel insights into better HCC management strategies.", "claims": [{"id": "claim-method", "statement": "Significant OS-related genes were selected (P<0.01) to further perform variable selection using Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis. The significant predictors were selected using 1 standard error (1-SE) of the minimum criteria. Then, multivariate survival analysis was performed by stepwise Cox proportional hazards regression model to determine the most useful prognostic genes and then NK cell marker genes-related prognostic signature (NKPS) was constructed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37554171", "locator": "sections[5] \"Establishment and validation of NK cell marker genes-related prognostic signature and nomogram construction\" paragraph 2", "quote": "Significant OS-related genes were selected (P<0.01) to further perform variable selection using Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis. The significant predictors were selected using 1 standard error (1-SE) of the minimum criteria. Then, multivariate survival analysis was performed by stepwise Cox proportional hazards regression model to determine the most useful prognostic genes and then NK cell marker genes-related prognostic signature (NKPS) was constructed."}], "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 authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37554171", "locator": "sections[26] \"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 authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study used scRNA-seq to identify NK-cell marker genes in 12 primary HCC samples, selected prognostic genes with LASSO-penalized and stepwise Cox regression analyses using TCGA data, and externally validated the resulting five-gene NKPS in the ICGC-LIHC, GSE14520, and Guilin cohorts.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37554171", "locator": "sections[15] \"Identification of NK cell marker genes expression profiles\" paragraph 2", "quote": "We first obtained single-cell transcriptomic profile data of 12 primary HCC samples, consisted of 10548 single cells from the CNP0000650 dataset."}, {"asset": "source:pmid:37554171", "locator": "sections[16] \"Construction of NK cell genes-related prognostic signature for the prognostic prediction of HCC\" paragraph 2", "quote": "After taking these 37 genes into the LASSO Cox regression model with minimized lambda, 12 NK cell marker genes were identified"}, {"asset": "source:pmid:37554171", "locator": "sections[16] \"Construction of NK cell genes-related prognostic signature for the prognostic prediction of HCC\" paragraph 2", "quote": "Five genes (LPCAT1, IL18RAP, SRSF2, ADGRG3, ADGRE5) ( Supplementary Figure S2D ) were identified to establish the NK cell marker genes-related prognostic signature (NKPS)."}, {"asset": "source:pmid:37554171", "locator": "sections[17] \"Validation of the NKPS in different clinical subgroups and external datasets\" paragraph 2", "quote": "The prognostic value of NKPS was evaluated in different age, gender, TNM stage, pathological stage, AFP level, and HBV or HCV infection subgroups."}, {"asset": "source:pmid:37554171", "locator": "sections[17] \"Validation of the NKPS in different clinical subgroups and external datasets\" paragraph 3", "quote": "To validate the prognostic performance of the NKPS in different data platforms, the GSE14520 dataset, ICGC dataset and Guilin cohort were used as external validation datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study used scRNA-seq to identify NK-cell marker genes in 12 primary HCC samples, selected prognostic genes with LASSO-penalized and stepwise Cox regression analyses using TCGA data, and externally validated the resulting five-gene NKPS in the ICGC-LIHC, GSE14520, and Guilin cohorts.", "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:37554171"], "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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