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Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma

BACKGROUND: The exact regulation network of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene expression profiles related to PD-1 as well as its ligands PD-L1 and PD-L2, thu...

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Autores principales: Sheng, Qiu-Ju, Tian, Wen-Yue, Dou, Xiao-Guang, Zhang, Chong, Li, Yan-Wei, Han, Chao, Fan, Yao-Xin, Lai, Ping-Ping, Ding, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667459/
https://www.ncbi.nlm.nih.gov/pubmed/33250959
http://dx.doi.org/10.4251/wjgo.v12.i11.1255
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author Sheng, Qiu-Ju
Tian, Wen-Yue
Dou, Xiao-Guang
Zhang, Chong
Li, Yan-Wei
Han, Chao
Fan, Yao-Xin
Lai, Ping-Ping
Ding, Yang
author_facet Sheng, Qiu-Ju
Tian, Wen-Yue
Dou, Xiao-Guang
Zhang, Chong
Li, Yan-Wei
Han, Chao
Fan, Yao-Xin
Lai, Ping-Ping
Ding, Yang
author_sort Sheng, Qiu-Ju
collection PubMed
description BACKGROUND: The exact regulation network of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene expression profiles related to PD-1 as well as its ligands PD-L1 and PD-L2, thus deciphering their possible biological processes in hepatocellular carcinoma (HCC). AIM: To find the possible mechanism of function of PD-1, PD-L1, and PD-L2 in HCC. METHODS: Based on the expression data of HCC from The Cancer Genome Atlas, the PD-1/PD-L1/PD-L2 related genes were screened by weighted correlation network analysis method and the biological processes of certain genes were enriched. Relation of PD1/PD-L1/PD-L2 with immune infiltration and checkpoints was investigated by co-expression analysis. The roles of PD-1/PD-L1/PD-L2 in determination of clinical outcome were also analyzed. RESULTS: Mutations of calcium voltage-gated channel subunit alpha1 E, catenin beta 1, ryanodine receptor 2, tumor suppressor protein p53, and Titin altered PD-1/PD-L1/PD-L2 expression profiles in HCC. PD-1, PD-L1, and PD-L2 related genes were mainly enriched in biological procedures of T cell activation, cell adhesion, and other important lymphocyte effects. In addition, PD-1/PD-L1/PD-L2 was related with immune infiltration of CD8 T cells, cytotoxic lymphocytes, fibroblasts, and myeloid dendritic cells. Immune checkpoints of CTLA4, CD27, CD80, CD86, and CD28 were significantly related to the PD-1/PD-L1/PD-L2 axis. Clinically, PD-1 and PD-L2 expression was correlated with recurrence (P = 0.005 for both), but there was no significant correlation between their expression and HCC patient survival. CONCLUSION: Mutations of key genes influence PD-1, PD-L1, and PD-L2 expression. PD-1, PD-L1, and PD-L2 related genes participate in T cell activation, cell adhesion, and other important lymphocyte effects. The finding that PD-1/PD-L1/PD-L2 is related to immune infiltration and other immune checkpoints would expand our understanding of promising anti-PD-1 immunotherapy.
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spelling pubmed-76674592020-11-27 Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma Sheng, Qiu-Ju Tian, Wen-Yue Dou, Xiao-Guang Zhang, Chong Li, Yan-Wei Han, Chao Fan, Yao-Xin Lai, Ping-Ping Ding, Yang World J Gastrointest Oncol Basic Study BACKGROUND: The exact regulation network of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene expression profiles related to PD-1 as well as its ligands PD-L1 and PD-L2, thus deciphering their possible biological processes in hepatocellular carcinoma (HCC). AIM: To find the possible mechanism of function of PD-1, PD-L1, and PD-L2 in HCC. METHODS: Based on the expression data of HCC from The Cancer Genome Atlas, the PD-1/PD-L1/PD-L2 related genes were screened by weighted correlation network analysis method and the biological processes of certain genes were enriched. Relation of PD1/PD-L1/PD-L2 with immune infiltration and checkpoints was investigated by co-expression analysis. The roles of PD-1/PD-L1/PD-L2 in determination of clinical outcome were also analyzed. RESULTS: Mutations of calcium voltage-gated channel subunit alpha1 E, catenin beta 1, ryanodine receptor 2, tumor suppressor protein p53, and Titin altered PD-1/PD-L1/PD-L2 expression profiles in HCC. PD-1, PD-L1, and PD-L2 related genes were mainly enriched in biological procedures of T cell activation, cell adhesion, and other important lymphocyte effects. In addition, PD-1/PD-L1/PD-L2 was related with immune infiltration of CD8 T cells, cytotoxic lymphocytes, fibroblasts, and myeloid dendritic cells. Immune checkpoints of CTLA4, CD27, CD80, CD86, and CD28 were significantly related to the PD-1/PD-L1/PD-L2 axis. Clinically, PD-1 and PD-L2 expression was correlated with recurrence (P = 0.005 for both), but there was no significant correlation between their expression and HCC patient survival. CONCLUSION: Mutations of key genes influence PD-1, PD-L1, and PD-L2 expression. PD-1, PD-L1, and PD-L2 related genes participate in T cell activation, cell adhesion, and other important lymphocyte effects. The finding that PD-1/PD-L1/PD-L2 is related to immune infiltration and other immune checkpoints would expand our understanding of promising anti-PD-1 immunotherapy. Baishideng Publishing Group Inc 2020-11-15 2020-11-15 /pmc/articles/PMC7667459/ /pubmed/33250959 http://dx.doi.org/10.4251/wjgo.v12.i11.1255 Text en ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
spellingShingle Basic Study
Sheng, Qiu-Ju
Tian, Wen-Yue
Dou, Xiao-Guang
Zhang, Chong
Li, Yan-Wei
Han, Chao
Fan, Yao-Xin
Lai, Ping-Ping
Ding, Yang
Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma
title Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma
title_full Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma
title_fullStr Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma
title_full_unstemmed Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma
title_short Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma
title_sort programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667459/
https://www.ncbi.nlm.nih.gov/pubmed/33250959
http://dx.doi.org/10.4251/wjgo.v12.i11.1255
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