High Expression of Hyaluronan-Mediated Motility Receptor Predicts Adverse Outcomes: A Potential Therapeutic Target for Head and Neck Squamous Cell Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33763352", "kind": "science-record", "revision": 7, "content_hash": "sha256:1872bd7bb59858cd50c40dece2d91c3b59be1a7179bfe058acdbc2080ab8af58", "created_at": "2026-11-01T15:41:30Z", "updated_at": "2026-11-01T22:03:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "High Expression of Hyaluronan-Mediated Motility Receptor Predicts Adverse Outcomes: A Potential Therapeutic Target for Head and Neck Squamous Cell Carcinoma.", "doi": "10.3389/fonc.2021.608842", "pmid": "33763352", "authors": ["Tianzhu Lu", "Yahan Zheng", "Xiaochang Gong", "Qiaoli Lv", "Junjun Chen", "Ziwei Tu", "Shaojun Lin", "Jianji Pan", "Qiaojuan Guo", "Jingao Li"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "Background: Several studies have shown that the hyaluronan-mediated motility receptor (HMMR) is overexpressed in various cancers and could be a potential prognostic factor. However, further research is still required to determine the prognostic value and potential function of HMMR in head and neck squamous cell carcinoma (HNSCC). Materials and Methods: Transcriptomic expression data were collected from the Cancer Genome Atlas database (TCGA) and Gene Expression Omnibus and the differences in HMMR expression between normal and tumor tissues were analyzed. The correlation between the methylation level of HMMR and its mRNA expression was analyzed via cBioPortal. Additionally, the data obtained from TCGA was analyzed with MethSurv to determine the prognostic value of the HMMR methylation levels in HNSCC. Gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to explore the potential biological functions of HMMR. Results: HMMR was highly expressed in HNSCC tumor tissue compared to normal tissue (p < 0.001). Multivariate analysis (MAV) showed that high HMMR mRNA expression was an independent prognostic factor of overall survival (OS) in TCGA (HR = 1.628, 95% CI: 1.169-2.266, p = 0.004) and GSE41613 data (HR = 2.238, p = 0.013). The methylation level of HMMR negatively correlated with the HMMR expression (R = -0.12, p < 0.001), and patients with low HMMR methylation had worse OS than patients with high methylation (p < 0.001). GSEA found that HMMR expression was associated with the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses, whereas ssGSEA showed that HMMR expression positively correlated with the infiltration level of Th2 cells. MAV confirmed that high HMMR protein expression was an inferior independent factor for OS (HR = 2.288, p = 0.045) and progression-free survival (HR = 2.247, p = 0.038) in 70 HNSCC. Conclusions: This study demonstrated that the upregulation of HMMR mRNA and protein in HNSCC is a biomarker for poor prognosis. The biological functions of HMMR are potentially related to the KARS, EMT, and G2M checkpoint pathways, as well as the interferon-gamma and interferon-alpha responses. These findings help to elucidate the role of HMMR in carcinogenesis and lay a foundation for further study.", "claims": [{"id": "claim-method", "statement": "The copy number variation (CNV) and methylation level data of HMMR were obtained through the cBioPortal web platform (https://www.cbioportal.org/) and a comparison of the varying HMMR gene expressions in HMMR copy number variation groups (Kruskal–Wallis test) and the correlation between HMMR methylation level and HMMR gene expression (Person correlation) was conducted.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33763352", "locator": "sections[8] \"HMMR Methylation Level and Its Prognosis Analysis\" paragraph 2", "quote": "The copy number variation (CNV) and methylation level data of HMMR were obtained through the cBioPortal web platform (https://www.cbioportal.org/) and a comparison of the varying HMMR gene expressions in HMMR copy number variation groups (Kruskal–Wallis test) and the correlation between HMMR methylation level and HMMR gene expression (Person correlation) was conducted."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33763352", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "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:33763352"], "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:GSE41613"], "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:GSE41613"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33763352", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2021.608842", "sha256": "sha256:4b0ce834ad27dc8bd84495bfe9f33b38d70dae0f6ffb44df39ae961073baec18", "bytes": 51426, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2021.608842", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7982417", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE41613", "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=GSE41613", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE41613", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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"format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:4aca92df547ee2f278fb703ca89219587cbfd8242e86520ae55d1000892386ac", "bytes": 2706, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#T1", "version": null, "note": "Demographic and clinical characteristics of HNSCC patients with low- and high expression HMMR in TCGA (n = 500).", "structure": {"pmcid": "PMC7982417", "section_index": 15, "section_title": "HMMR Was Upregulated in HNSCC", "row_count": 53, "column_count": 5}, "table": {"label": "Table 1", "caption": "Demographic and clinical characteristics of HNSCC patients with low- and high expression HMMR in TCGA (n = 500).", "rows": [["Characters", "Level", "HMMR expression", "p"], ["", "", "Low (n = 250)", "High (n−250)", ""], ["Gender (%)", "Female", "70 (28.0%)", "63 (25.2%)", "0.544"], ["", "Male", "180 (72.0%)", "187 (74.8%)", ""], ["Age (median 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GSE41613 (n = 97).", "rows": [["Characteristics", "Univariate analysis", "Multivariate analysis"], ["", "HR (95% CI)", "P-value", "HR (95% CI)", "P-value"], ["Clinical stage (I–II vs. III–IV)", "3.828 (1.958–7.482)", "<0.001", "6.078 (2.603–14.919)", "<0.001"], ["Age (≤ 60 vs. >60)", "0.739 (0.423–1.292)", "0.289", "", ""], ["Gender (Female vs. Male)", "0.891 (0.493–1.611)", "0.703", "", ""], ["Comprehensive treatment (No vs. Yes)", "1.671 (0.939–2.974)", "0.081", "0.532 (0.256–1.104)", "0.090"], ["HMMR (Low vs. High)", "2.240 (1.189–4.221)", "0.013", "2.238 (1.187–4.221)", "0.013"]], "row_count": 7, "column_count": 5, "numeric_cells": 19, "header_rows": 2, "locator": "section[16]/table-wrap[2]#T3"}}, {"id": "asset:table:pmid:33763352:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:aaee9899b094d3518454db70bdc9a918df0f105606e12b98368a59bffe926e9a", "bytes": 1474, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[19]/table-wrap[1]#T4", "version": null, "note": "Hallmark Pathways enriched in high- and low-risk groups by using GSEA.", "structure": {"pmcid": "PMC7982417", "section_index": 19, "section_title": "Functional Enrichment Analysis of High- and Low-HMMR Expression Samples", "row_count": 20, "column_count": 5}, "table": {"label": "Table 4", "caption": "Hallmark Pathways enriched in high- and low-risk groups by using GSEA.", "rows": [["ID", "NES", "p value", "p.adjust", "FDR"], ["HALLMARK_KRAS_SIGNALING_DN", "−1.909", "0.001", "0.027", "0.018"], ["HALLMARK_MYOGENESIS", "−2.822", "0.001", "0.027", "0.018"], ["HALLMARK_PANCREAS_BETA_CELLS", "1.692", "0.004", "0.045", "0.03"], ["HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION", "−1.55", "0.004", "0.045", "0.03"], ["HALLMARK_MYC_TARGETS_V2", "1.722", "0.005", "0.045", "0.03"], ["HALLMARK_SPERMATOGENESIS", "2.529", "0.009", "0.047", "0.031"], ["HALLMARK_E2F_TARGETS", "4.224", "0.012", "0.047", "0.031"], ["HALLMARK_G2M_CHECKPOINT", "3.904", "0.012", "0.047", "0.031"], ["HALLMARK_INTERFERON_GAMMA_RESPONSE", "1.679", "0.012", "0.047", "0.031"], ["HALLMARK_MTORC1_SIGNALING", "1.524", "0.012", "0.047", "0.031"], ["HALLMARK_MYC_TARGETS_V1", "1.971", "0.012", "0.047", "0.031"], ["HALLMARK_MITOTIC_SPINDLE", "2.916", "0.012", "0.047", "0.031"], ["HALLMARK_INTERFERON_ALPHA_RESPONSE", "1.834", "0.012", "0.047", "0.031"], ["HALLMARK_INFLAMMATORY_RESPONSE", "1.268", "0.024", "0.084", "0.055"], ["HALLMARK_ANDROGEN_RESPONSE", "1.51", "0.025", "0.084", "0.055"], ["HALLMARK_APICAL_SURFACE", "−1.518", "0.034", "0.105", "0.069"], ["HALLMARK_ALLOGRAFT_REJECTION", "1.248", "0.036", "0.105", "0.069"], ["HALLMARK_P53_PATHWAY", "−1.331", "0.044", "0.12", "0.079"], ["HALLMARK_IL6_JAK_STAT3_SIGNALING", "1.396", "0.046", "0.12", "0.079"]], "row_count": 20, "column_count": 5, "numeric_cells": 77, "header_rows": 1, "locator": "section[19]/table-wrap[1]#T4"}}, {"id": 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(7.4%)", "3 (7.0%)", "0.999"], ["", "Male", "25 (92.6%)", "40 (93.0%)", ""], ["Age", "<60 years", "15 (55.6%)", "17 (39.5%)", "0.685"], ["", "≥60 years", "12 (44.4%)", "26 (60.5%)", ""], ["T classification", "T1–T2", "13 (48.1%)", "17 (39.5%)", "0.478"], ["", "T3–T4", "14 (51.9%)", "26 (60.5%)", ""], ["N classification", "N0–1", "24 (88.9%)", "31 (72.1%)", "0.137"], ["", "N2–3", "3 (11.1%)", "12 (27.9%)", ""], ["Clinical stage", "Stage I–II", "12 (44.4%)", "14 (32.6%)", "0.316"], ["", "Stage III–IV", "15 (55.6%)", "29 (67.4%)", ""], ["Histologic grade", "G1", "16 (59.3%)", "13 (30.2%)", "0.055"], ["", "G2", "6 (22.2%)", "15 (34.9%)", ""], ["", "G3", "6 (18.5%)", "15 (34.9%)", ""], ["Anatomic site", "Oral cavity", "8 (29.6%)", "7 (16.3%)", "0.549"], ["", "Oropharynx", "1 (3.7%)", "3 (7.0%)", ""], ["", "Hypopharynx", "1 (3.7%)", "3 (7.0%)", ""], ["", "Larynx", "17 (63.0%)", "30 (67.8%)", ""]], "row_count": 19, "column_count": 5, "numeric_cells": 47, "header_rows": 2, "locator": "section[21]/table-wrap[1]#T5"}}, {"id": "asset:table:pmid:33763352:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c98e71c35acdbb11f3e3d379a20e369acc03463bf588a837e87abf78f52c5e82", "bytes": 1038, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[21]/table-wrap[2]#T6", "version": null, "note": "The multivariate analyses of overall survival and progression-free survival according to HMMR protein expression, after adjusting for other potential predictors (n = 70).", "structure": {"pmcid": "PMC7982417", "section_index": 21, "section_title": "Validation the HMMR Expression and Prognostic Value of HMMR in HNSCC", "row_count": 8, "column_count": 5}, "table": {"label": "Table 6", "caption": "The multivariate analyses of overall survival and progression-free survival according to HMMR protein expression, after adjusting for other potential predictors (n = 70).", "rows": [["Characteristics", "Overall survival", "Multivariate analysis"], ["", "HR (95% CI)", "P-value", "HR (95% CI)", "P-value"], ["Clinical stage (I–IIvs. III–IV)", "2.644 (0.966–7.234)", "0.058", "3.109 (1.157–8.353)", "0.024"], ["Age (≤ 60 vs. >60)", "1.270 (0.600–2.689)", "0.533", "1.296 (0.635–2.647)", "0.476"], ["Gender (Female vs. Male)", "0.754 (0.076–7.516)", "0.810", "0.688 (0.071–6.646)", "0.747"], ["Histologic grade (G1 vs. G2/G3)", "1.075 (0.514–2.249)", "0.848", "1.134 (0.559–2.298)", "0.728"], ["Anatomic site (Oral cavity/Oropharynx/Hypopharynx vs. Larynx)", "2.049 (0.782–5.371)", "0.144", "1.949 (0.802–4.737)", "0.141"], ["HMMR (Low vs. High)", "2.288 (1.019–5.137)", "0.045", "2.247 (1.048–4.817)", "0.038"]], "row_count": 8, "column_count": 5, "numeric_cells": 27, "header_rows": 2, "locator": "section[21]/table-wrap[2]#T6"}}], "gaps": ["asset:data:geo:GSE41613 not downloaded", "asset:data:geo:GSE41613 licence not read"]}, "analysis": {"state": "partial", 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