Clinical Significance of the HHLA2 Protein in Hepatocellular Carcinoma and the Tumor Microenvironment

Min Luo,1 Yan Lin,1 Rong Liang,1 Yongqiang Li,1 Lianying Ge2 1Department of Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of...

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Autores principales:	Luo M, Lin Y, Liang R, Li Y, Ge L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	hepatocellular carcinoma hhla2 tumor-infiltrating lymphocyte tumor microenvironment Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/8361f04435544b848065650b96ddd552
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spelling	oai:doaj.org-article:8361f04435544b848065650b96ddd5522021-12-02T16:33:57ZClinical Significance of the HHLA2 Protein in Hepatocellular Carcinoma and the Tumor Microenvironment1178-7031https://doaj.org/article/8361f04435544b848065650b96ddd5522021-08-01T00:00:00Zhttps://www.dovepress.com/clinical-significance-of-the-hhla2-protein-in-hepatocellular-carcinoma-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Min Luo,1 Yan Lin,1 Rong Liang,1 Yongqiang Li,1 Lianying Ge2 1Department of Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Yongqiang LiDepartment of Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of ChinaEmail lyq702702@126.comLianying GeDepartment of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of ChinaEmail gxgly@hotmail.comBackground: The protein “human endogenous retrovirus H long terminal repeat-associating 2” (HHLA2), a member of the B7 family, has been linked to cancer progression and immune responses. However, its functional role in hepatocellular carcinoma (HCC) remains unknown.Methods: Bioinformatics was used to examine the potential roles of HHLA2 in HCC and the molecular pathways involved. Expression of HHLA2 and PD-L1 as well as the density of tumor-infiltrating lymphocytes (TILs) in tumoral areas were evaluated by immunohistochemistry and hematoxylin-eosin staining of 202 resected human HCC samples. Potential correlations of HHLA2 expression with pathological characteristics or prognosis of HCC patients were explored. Different types of immune microenvironment in HCC were defined based on HHLA2 expression and TIL density.Results: High HHLA2 levels in HCC correlated with more advanced clinical cancer stage (P = 0.040), multiple tumors (P = 0.044), poor tumor differentiation (P = 0.048), microvascular invasion (P = 0.011) and hepatic capsule invasion (P = 0.047). HHLA2 levels correlated significantly with density of TILs, but not with PD-L1 levels. High HHLA2 levels were associated with worse prognosis. Intermediate and high TIL densities were independent predictors of better prognosis. Tumor microenvironments with type I (HHLA2 - high TILs +) or type IV (HHLA2 - low TILs +) were associated with better prognosis.Conclusion: HHLA2 level can independently predict worse prognosis and affect the tumor microenvironment in HCC, which may help guide immunotherapy against the cancer.Keywords: hepatocellular carcinoma, HHLA2, tumor-infiltrating lymphocyte, tumor microenvironmentLuo MLin YLiang RLi YGe LDove Medical Pressarticlehepatocellular carcinomahhla2tumor-infiltrating lymphocytetumor microenvironmentPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4217-4228 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatocellular carcinoma hhla2 tumor-infiltrating lymphocyte tumor microenvironment Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	hepatocellular carcinoma hhla2 tumor-infiltrating lymphocyte tumor microenvironment Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Luo M Lin Y Liang R Li Y Ge L Clinical Significance of the HHLA2 Protein in Hepatocellular Carcinoma and the Tumor Microenvironment
description	Min Luo,1 Yan Lin,1 Rong Liang,1 Yongqiang Li,1 Lianying Ge2 1Department of Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Yongqiang LiDepartment of Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of ChinaEmail lyq702702@126.comLianying GeDepartment of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning, 530021, People’s Republic of ChinaEmail gxgly@hotmail.comBackground: The protein “human endogenous retrovirus H long terminal repeat-associating 2” (HHLA2), a member of the B7 family, has been linked to cancer progression and immune responses. However, its functional role in hepatocellular carcinoma (HCC) remains unknown.Methods: Bioinformatics was used to examine the potential roles of HHLA2 in HCC and the molecular pathways involved. Expression of HHLA2 and PD-L1 as well as the density of tumor-infiltrating lymphocytes (TILs) in tumoral areas were evaluated by immunohistochemistry and hematoxylin-eosin staining of 202 resected human HCC samples. Potential correlations of HHLA2 expression with pathological characteristics or prognosis of HCC patients were explored. Different types of immune microenvironment in HCC were defined based on HHLA2 expression and TIL density.Results: High HHLA2 levels in HCC correlated with more advanced clinical cancer stage (P = 0.040), multiple tumors (P = 0.044), poor tumor differentiation (P = 0.048), microvascular invasion (P = 0.011) and hepatic capsule invasion (P = 0.047). HHLA2 levels correlated significantly with density of TILs, but not with PD-L1 levels. High HHLA2 levels were associated with worse prognosis. Intermediate and high TIL densities were independent predictors of better prognosis. Tumor microenvironments with type I (HHLA2 - high TILs +) or type IV (HHLA2 - low TILs +) were associated with better prognosis.Conclusion: HHLA2 level can independently predict worse prognosis and affect the tumor microenvironment in HCC, which may help guide immunotherapy against the cancer.Keywords: hepatocellular carcinoma, HHLA2, tumor-infiltrating lymphocyte, tumor microenvironment
format	article
author	Luo M Lin Y Liang R Li Y Ge L
author_facet	Luo M Lin Y Liang R Li Y Ge L
author_sort	Luo M
title	Clinical Significance of the HHLA2 Protein in Hepatocellular Carcinoma and the Tumor Microenvironment
title_short	Clinical Significance of the HHLA2 Protein in Hepatocellular Carcinoma and the Tumor Microenvironment
title_full	Clinical Significance of the HHLA2 Protein in Hepatocellular Carcinoma and the Tumor Microenvironment
title_fullStr	Clinical Significance of the HHLA2 Protein in Hepatocellular Carcinoma and the Tumor Microenvironment
title_full_unstemmed	Clinical Significance of the HHLA2 Protein in Hepatocellular Carcinoma and the Tumor Microenvironment
title_sort	clinical significance of the hhla2 protein in hepatocellular carcinoma and the tumor microenvironment
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/8361f04435544b848065650b96ddd552
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Clinical Significance of the HHLA2 Protein in Hepatocellular Carcinoma and the Tumor Microenvironment

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