Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35986302", "kind": "science-record", "revision": 4, "content_hash": "sha256:caa814cf71ddd9e66f7e457c449f94af8028d776eb6efe30deeec599f7820bd2", "created_at": "2026-11-01T18:15:07Z", "updated_at": "2026-11-01T22:07:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma.", "doi": "10.1186/s12885-022-09999-y", "pmid": "35986302", "authors": ["Shengkui Tan", "Xuefeng Guo", "Chunhua Bei", "Huixia Zhang", "Di Li", "Xiaonian Zhu", "Hongzhuan Tan"], "journal": "BMC cancer", "year": 2022, "abstract": "BACKGROUND: Previous study has shown that chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) can bind and maintain programmed cell death ligand 1 (PD-L1) expression to promote tumor progression by alleviating the suppression of tumor-specific T cell activity, suggesting its potential role in tumor immunotherapy. However, the role of CMTM4 in tumor immunity has not been well clarified, especially in hepatocellular carcinoma (HCC).\nMETHODS: The protein expression of CMTM4/PD-L1/CD4/CD8 was detected by immunohistochemistry (IHC) detection in 90 cases of HCC tissues. The mRNA expression profiles and related prognosis data were obtained from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC). Two immune therapy cohorts were from Imvigor210 and GSE176307.\nRESULTS: Though the single protein expression of CMTM4, PD-L1, CD4 or CD8 in HCC tissues by IHC detection didn't show a significant relationship with the prognosis of HCC patients, we found that high co-expression of CMTM4/PD-L1/CD4 showed a good prognosis of HCC patients. Further Timer 2.0 analysis identified that HCC patients with high expression of CMTM4/PD-L1 and high infiltration of CD4+ T cells had a better overall survival than those with low infiltration of CD4+ T cells. Moreover, a series of bioinformatics analyses revealed that CMTM4-related genes posed important effects on prognosis and immunity in HCC patients, and CMTM4 had a positive correlation with infiltration of CD4+ and CD8+ T cells in HCC. At last, we used two immunotherapy cohorts to verify that the combination of CMTM4 with PD-L1 could improve the prognosis of tumor patients underwent immunotherapy.\nCONCLUSIONS: CMTM4 and PD-L1 co-expression with T cell infiltration shows prognostic significance in HCC, suggesting combined effect from multiple proteins should be considered in HCC treatment.", "claims": [{"id": "claim-method", "statement": "In order to construct an efficient CMTM4 prediction model, we used the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression to select the significant independent prognostic markers with P value less than 0.05 for overall survival (OS) in TCGA-LIHC [29].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35986302", "locator": "sections[9] \"Identification of CMTM4 related prognostic genes in HCC\" paragraph 2", "quote": "In order to construct an efficient CMTM4 prediction model, we used the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression to select the significant independent prognostic markers with P value less than 0.05 for overall survival (OS) in TCGA-LIHC [29]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. The RNA sequencing data from CMTM4 knockdown (KD) Hep3B cells can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186815.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35986302", "locator": "sections[27] \"Availability of data and materials\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. The RNA sequencing data from CMTM4 knockdown (KD) Hep3B cells can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE186815."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The AUC value was 0.886 from time-dependent ROC curve, suggesting its well prediction ability (Fig. 3H).", "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:35986302"], "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:GSE176307"], "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:GSE176307"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35986302", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-022-09999-y", "sha256": "sha256:924adeab14823cb555302713782528c18713ada605f8677010f8280bb240571e", "bytes": 55108, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12885-022-09999-y", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9389844", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE176307", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE176307", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE176307", "version": null, "note": "Publicly available datasets were analyzed in this study. 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The m", "f CMTM4, PD-L1, CD4 or CD8 in HCC tissues by IHC detection didn't show a significant relation", "-L1 samples were excluded due to the loss of immunohistochemical (IHC) sites during IHC quality control. One"], "order_basis": "paper_text_order:595", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["le datasets were analyzed in this study. The RNA sequencing data from CMTM4 knockdown (KD) Hep3B cells c"], "order_basis": "paper_text_order:3147", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["is study. The RNA sequencing data from CMTM4 knockdown (KD) Hep3B cells can be found here: https://"], "order_basis": "paper_text_order:3178", "id": "assay:3"}, {"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": ["In order to construct an efficient CMTM4 prediction model, we used the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression to select the significant independent prognostic markers with P value less than 0.05 for overall survival (OS) in TCGA-LIHC [29]."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}