{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:00:09Z","timestamp":1787068809253,"version":"build-2736575974"},"reference-count":42,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CBM"],"published-print":{"date-parts":[[2023,10,13]]},"abstract":"<jats:p>BACKGROUND: Lymphoid-specific helicase (HELLS), a SNF2-like chromatin-remodeling enzyme, plays a key role in tumor progression via its DNA methylation function. However, the effects of HELLS on immune infiltration and prognosis in liver hepatocellular carcinoma (LIHC) remain uncertain. METHODS: The Tumor Immune Estimation Resource (TIMER) database was employed to explore the pan-cancer mRNA expression of HELLS and its correlation with immunity. GEPIA2 was used to verify the correlation between HELLS expression and survival. The role of HELLS in cancer was explored via gene set enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) and the construction of gene-gene and protein-protein interaction networks (PPI). Additionally, correlations between DNA methylation, HELLS expression, and immune-related genes were explored in LIHC. HELLS expression in LIHC clinical samples was determined using qRT-PCR and western blotting. The effects of downregulated HELLS expression in hepatocellular carcinoma cells was explored via transfection experiments in vitro. RESULTS: High HELLS mRNA expression was identified in several cancers and was significantly associated with poorer prognosis in LIHC. Furthermore, HELLS expression was positively correlated with tumor-infiltrating lymphocytes and immune checkpoint genes in LIHC. Bioinformatics analysis suggested that DNA methylation of HELLS may be associated with the immune response. Results from the TCGA-LIHC dataset, clinical samples, and functional analysis indicated that HELLS contributed to tumor progression in LIHC. CONCLUSION: The study findings demonstrate that HELLS is an important factor in promoting LIHC malignancy and might serve as a potential biomarker for LIHC.<\/jats:p>","DOI":"10.3233\/cbm-230073","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T12:34:44Z","timestamp":1691152484000},"page":"225-239","source":"Crossref","is-referenced-by-count":3,"title":["Immunological function and prognostic value of lymphoid-specific helicase in liver hepatocellular carcinoma"],"prefix":"10.1177","volume":"38","author":[{"given":"Yuan","family":"Fang","sequence":"first","affiliation":[{"name":"Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"},{"name":"Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqiang","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China"},{"name":"Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"},{"name":"Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Head and Neck Surgery, Baoshan People\u2019s Hospital, Baoshang, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jin","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitao","family":"Li","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benkai","family":"Wei","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinglei","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan, China"},{"name":"Yunnan Province Clinical Research Center for Digestive Diseases, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanfei","family":"Huang","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"issue":"6","key":"10.3233\/CBM-230073_ref1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"issue":"1","key":"10.3233\/CBM-230073_ref2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21387","article-title":"Cancer Statistics.","volume":"67","author":"Siegel","year":"2017","journal-title":"CA Cancer J Clin"},{"issue":"4","key":"10.3233\/CBM-230073_ref3","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1002\/hep.30633","article-title":"Adjuvant Treatment of Hepatocellular Carcinoma: Prospect of Immunotherapy.","volume":"70","author":"Brown","year":"2019","journal-title":"Hepatology"},{"key":"10.3233\/CBM-230073_ref4","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.canlet.2019.12.002","article-title":"Immunotherapy for hepatocellular carcinoma","volume":"470","author":"Zongyi","year":"2020","journal-title":"Cancer Lett"},{"issue":"1","key":"10.3233\/CBM-230073_ref5","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1128\/MCB.01073-07","article-title":"LSH cooperates with DNA methyltransferases to repress transcription.","volume":"28","author":"Myant","year":"2008","journal-title":"Mol Cell Biol"},{"issue":"1","key":"10.3233\/CBM-230073_ref6","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41392-020-00249-w","article-title":"The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties","volume":"5","author":"Liu","year":"2020","journal-title":"Signal Transduct Target Ther"},{"issue":"4","key":"10.3233\/CBM-230073_ref7","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1038\/emboj.2011.451","article-title":"The SNF2-like helicase HELLS mediates E2F3-dependent transcription and cellular transformation.","volume":"31","author":"von Eyss","year":"2012","journal-title":"Embo J"},{"issue":"7","key":"10.3233\/CBM-230073_ref8","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.trecan.2020.02.003","article-title":"Cancer Epigenetics, Tumor Immunity, and Immunotherapy.","volume":"6","author":"Cao","year":"2020","journal-title":"Trends Cancer"},{"issue":"3","key":"10.3233\/CBM-230073_ref9","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/hep.29904","article-title":"Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification.","volume":"68","author":"Kurebayashi","year":"2018","journal-title":"Hepatology"},{"key":"10.3233\/CBM-230073_ref10","doi-asserted-by":"crossref","first-page":"796647","DOI":"10.3389\/fimmu.2021.796647","article-title":"A Pan-Cancer Analysis of Predictive Methylation Signatures of Response to Cancer Immunotherapy.","volume":"12","author":"Xu","year":"2021","journal-title":"Front Immunol"},{"issue":"21","key":"10.3233\/CBM-230073_ref11","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1158\/0008-5472.CAN-17-0307","article-title":"TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.","volume":"77","author":"Li","year":"2017","journal-title":"Cancer Res"},{"issue":"W1","key":"10.3233\/CBM-230073_ref12","doi-asserted-by":"crossref","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis.","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"10.3233\/CBM-230073_ref13","doi-asserted-by":"crossref","first-page":"D956","DOI":"10.1093\/nar\/gkx1090","article-title":"LinkedOmics: analyzing multi-omics data within and across 32 cancer types.","volume":"46","author":"Vasaikar","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"10.3233\/CBM-230073_ref14","doi-asserted-by":"crossref","unstructured":"Gene Ontology Consortium: going forward. Nucleic Acids Res 43 (Database issue) (2015), D1049\u201356.","DOI":"10.1093\/nar\/gku1179"},{"issue":"D1","key":"10.3233\/CBM-230073_ref15","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: new perspectives on genomes, pathways, diseases and drugs.","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"10.3233\/CBM-230073_ref16","doi-asserted-by":"crossref","first-page":"W214","DOI":"10.1093\/nar\/gkq537","article-title":"The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function.","volume":"38","author":"Warde-Farley","year":"2010","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"10.3233\/CBM-230073_ref17","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets.","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"10.3233\/CBM-230073_ref18","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection.","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst"},{"issue":"8","key":"10.3233\/CBM-230073_ref19","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.neo.2017.05.002","article-title":"UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses.","volume":"19","author":"Chandrashekar","year":"2017","journal-title":"Neoplasia"},{"issue":"5","key":"10.3233\/CBM-230073_ref20","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data.","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov"},{"key":"10.3233\/CBM-230073_ref21","doi-asserted-by":"crossref","first-page":"745166","DOI":"10.3389\/fonc.2021.745166","article-title":"A Co-Expression Network Reveals the Potential Regulatory Mechanism of lncRNAs in Relapsed Hepatocellular Carcinoma.","volume":"11","author":"Fang","year":"2021","journal-title":"Front Oncol"},{"issue":"5","key":"10.3233\/CBM-230073_ref22","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1142\/S0192415X20500573","article-title":"Gastrodin Pretreatment Protects Liver Against Ischemia-Reperfusion Injury via Activation of the Nrf2\/HO-1 Pathway.","volume":"48","author":"Yuan","year":"2020","journal-title":"Am J Chin Med"},{"key":"10.3233\/CBM-230073_ref23","doi-asserted-by":"crossref","unstructured":"P. Federico, A. Petrillo, P. Giordano, D. Bosso, A. Fabbrocini, M. Ottaviano, M. Rosanova, A. Silvestri, A. Tufo, A. Cozzolino and B. Daniele, Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Status and Novel Perspectives. Cancers (Basel) 12(10) (2020).","DOI":"10.3390\/cancers12103025"},{"key":"10.3233\/CBM-230073_ref24","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ejca.2020.08.024","article-title":"Immune scores in colorectal cancer: Where are we?","volume":"140","author":"Malka","year":"2020","journal-title":"Eur J Cancer"},{"issue":"5","key":"10.3233\/CBM-230073_ref25","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.apsb.2019.09.006","article-title":"Epigenetic strategies synergize with PD-L1\/PD-1 targeted cancer immunotherapies to enhance antitumor responses.","volume":"10","author":"Chen","year":"2020","journal-title":"Acta Pharm Sin B"},{"issue":"1","key":"10.3233\/CBM-230073_ref26","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41419-021-03425-0","article-title":"The DNA-helicase HELLS drives ALK(-) ALCL proliferation by the transcriptional control of a cytokinesis-related program.","volume":"12","author":"Tameni","year":"2021","journal-title":"Cell Death Dis"},{"issue":"1","key":"10.3233\/CBM-230073_ref27","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/cam4.3627","article-title":"HELLS, a chromatin remodeler is highly expressed in pancreatic cancer and downregulation of it impairs tumor growth and sensitizes to cisplatin by reexpressing the tumor suppressor TGFBR3.","volume":"10","author":"Hou","year":"2021","journal-title":"Cancer Med"},{"issue":"1","key":"10.3233\/CBM-230073_ref28","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12920-021-01043-5","article-title":"HELLS serves as a poor prognostic biomarker and its downregulation reserves the malignant phenotype in pancreatic cancer.","volume":"14","author":"Wang","year":"2021","journal-title":"BMC Med Genomics"},{"issue":"22","key":"10.3233\/CBM-230073_ref29","doi-asserted-by":"crossref","first-page":"e2101672","DOI":"10.1002\/advs.202101672","article-title":"Targeted Anti-Tumor Immunotherapy Using Tumor Infiltrating Cells.","volume":"8","author":"Xie","year":"2021","journal-title":"Adv Sci (Weinh)"},{"issue":"6","key":"10.3233\/CBM-230073_ref30","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1159\/000518104","article-title":"Immune Checkpoint Inhibitors: The Emerging Cornerstone in Cholangiocarcinoma Therapy?","volume":"10","author":"Guti\u00e9rrez-Larra\u00f1aga","year":"2021","journal-title":"Liver Cancer"},{"issue":"1","key":"10.3233\/CBM-230073_ref31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13045-021-01134-x","article-title":"Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities.","volume":"14","author":"Liu","year":"2021","journal-title":"J Hematol Oncol"},{"issue":"3","key":"10.3233\/CBM-230073_ref32","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/nrc.2017.121","article-title":"Targeting B cell receptor signalling in cancer: preclinical and clinical advances.","volume":"18","author":"Burger","year":"2018","journal-title":"Nat Rev Cancer"},{"issue":"11","key":"10.3233\/CBM-230073_ref33","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.it.2021.09.004","article-title":"Staggered starts in the race to T cell activation.","volume":"42","author":"Richard","year":"2021","journal-title":"Trends Immunol"},{"issue":"1","key":"10.3233\/CBM-230073_ref34","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12929-017-0329-9","article-title":"Cancer immunotherapies targeting the PD-1 signaling pathway.","volume":"24","author":"Iwai","year":"2017","journal-title":"J Biomed Sci"},{"issue":"1","key":"10.3233\/CBM-230073_ref35","doi-asserted-by":"crossref","first-page":"2002068","DOI":"10.1080\/2162402X.2021.2002068","article-title":"PD-1 blockade improves the anti-tumor potency of exhausted CD3(+)CD56(+) NKT-like cells in patients with primary hepatocellular carcinoma.","volume":"10","author":"Tao","year":"2021","journal-title":"Oncoimmunology"},{"key":"10.3233\/CBM-230073_ref36","doi-asserted-by":"crossref","first-page":"708819","DOI":"10.3389\/fcell.2021.708819","article-title":"Combined DNA Methylation and Transcriptomic Assessments to Determine a Prognostic Model for PD-1-Negative Hepatocellular Carcinoma.","volume":"9","author":"Zhu","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"2","key":"10.3233\/CBM-230073_ref37","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41389-020-0210-7","article-title":"Chromatin remodeling protein HELLS is critical for retinoblastoma tumor initiation and progression.","volume":"9","author":"Zocchi","year":"2020","journal-title":"Oncogenesis"},{"issue":"21","key":"10.3233\/CBM-230073_ref38","doi-asserted-by":"crossref","first-page":"12116","DOI":"10.1093\/nar\/gkaa1003","article-title":"A role for LSH in facilitating DNA methylation by DNMT1 through enhancing UHRF1 chromatin association.","volume":"48","author":"Han","year":"2020","journal-title":"Nucleic Acids Res"},{"issue":"16","key":"10.3233\/CBM-230073_ref39","doi-asserted-by":"crossref","first-page":"7592","DOI":"10.1093\/nar\/gkw424","article-title":"The SNF2 family ATPase LSH promotes cell-autonomous de novo DNA methylation in somatic cells.","volume":"44","author":"Termanis","year":"2016","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"10.3233\/CBM-230073_ref40","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1186\/s12967-018-1732-z","article-title":"Integrated analysis of dysregulated long non-coding RNAs\/microRNAs\/mRNAs in metastasis of lung adenocarcinoma.","volume":"16","author":"Li","year":"2018","journal-title":"J Transl Med"},{"key":"10.3233\/CBM-230073_ref41","doi-asserted-by":"crossref","first-page":"10153","DOI":"10.2147\/OTT.S223668","article-title":"Downregulation of the Helicase Lymphoid-Specific (HELLS) Gene Impairs Cell Proliferation and Induces Cell Cycle Arrest in Colorectal Cancer Cells.","volume":"12","author":"Liu","year":"2019","journal-title":"Onco Targets Ther"},{"issue":"1","key":"10.3233\/CBM-230073_ref42","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ijc.20407","article-title":"Tumor-specific exon creation of the HELLS\/SMARCA6 gene in non-small cell lung cancer.","volume":"112","author":"Yano","year":"2004","journal-title":"Int J Cancer"}],"container-title":["Cancer Biomarkers"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/CBM-230073","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:10:20Z","timestamp":1777385420000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/CBM-230073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,13]]},"references-count":42,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/cbm-230073","relation":{},"ISSN":["1875-8592","1574-0153"],"issn-type":[{"value":"1875-8592","type":"electronic"},{"value":"1574-0153","type":"print"}],"subject":[],"published":{"date-parts":[[2023,10,13]]}}}