{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:52:20Z","timestamp":1772160740293,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2024,2]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n The incidence and mortality of tongue squamous cell carcinoma have shown an alarming increase in recent years. This study aimed to investigate the potential of\n HHLA2<\/jats:italic>\n as an immune checkpoint in comparison to PD\u2010L1.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We obtained RNA\u2010seq data from TCGA to study\n HHLA2<\/jats:italic>\n and PD\u2010L1 expression across various tissues. Using the CIBERSORT package, we estimated cell type abundances within mixed populations based on gene expression profiles. Immunohistochemistry was performed to analyze\n HHLA2<\/jats:italic>\n and PD\u2010L1 expression in Tongue squamous cell carcinoma. Prognostic evaluation was carried out with Kaplan\u2013Meier curves and the log\u2010rank test. To explore factors affecting\n HHLA2<\/jats:italic>\n , univariate and multivariate Cox regression analyses were conducted with the COX regression model. Additionally, we used single\u2010cell RNA sequencing data from the GEO database for gene set enrichment analysis with genes strongly correlated with\n HHLA2<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Our analysis of RNA\u2010seq data unveiled a significant upregulation of\n HHLA2<\/jats:italic>\n and PD\u2010L1 expression in primary tumors when compared with normal tissue.\n HHLA2<\/jats:italic>\n exhibited a positive expression rate of 36.9%, while PD\u2010L1 had a positive expression rate of 24.6%.\n HHLA2<\/jats:italic>\n emerged as a noteworthy independent risk factor impacting the overall survival of Tongue squamous cell carcinoma patients. The analysis of scRNA\u2010seq data shed light on the involvement of\n HHLA2<\/jats:italic>\n in key pathways related to cell cycle regulation and interferon alpha\/beta signaling.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This study suggests that in the context of Tongue squamous cell carcinoma,\n HHLA2<\/jats:italic>\n may represent a more promising target for immunotherapy when compared with PD\u2010L1.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jop.13514","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T03:22:42Z","timestamp":1707276162000},"page":"159-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\n HHLA2<\/i>\n <\/scp>\n is more significantly associated with poor prognosis in\n TSCC<\/scp>\n than\n PD\u2010L1<\/scp>"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4400-652X","authenticated-orcid":false,"given":"Yi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery The Third Affiliated Hospital of Soochow University Changzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery The Third Affiliated Hospital of Soochow University Changzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery The Third Affiliated Hospital of Soochow University Changzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery 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