Correlation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinoma

Abstract Background MKI67 plays a vital role in the tumour microenvironment (TME) and congenital immunity. The present work focuses on exploring the prognosis prediction performance of MKI67 and its associations with T cell activity and immune infiltration within numerous cancers, especially hepatoc...

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Autores principales:	Shi-yi Wu, Pan Liao, Lu-yu Yan, Qian-yi Zhao, Zhao-yu Xie, Jie Dong, Hong-tao Sun
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Immunotherapy Immune infiltration T cells exhaustion Prognosis MKI67 Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/cc7537cd99fc4c1ba0a4be3217c384c9
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spelling	oai:doaj.org-article:cc7537cd99fc4c1ba0a4be3217c384c92021-11-08T10:45:44ZCorrelation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinoma10.1186/s12876-021-01984-21471-230Xhttps://doaj.org/article/cc7537cd99fc4c1ba0a4be3217c384c92021-11-01T00:00:00Zhttps://doi.org/10.1186/s12876-021-01984-2https://doaj.org/toc/1471-230XAbstract Background MKI67 plays a vital role in the tumour microenvironment (TME) and congenital immunity. The present work focuses on exploring the prognosis prediction performance of MKI67 and its associations with T cell activity and immune infiltration within numerous cancers, especially hepatocellular liver carcinoma (LIHC). Methods Oncomine, GEPIA2, and HPA were adopted to analyse MKI67 levels in different types of cancers. The prognostic prediction performance of MKI67 was evaluated through the TCGA portal, GEPIA2, LOGpc, and Kaplan–Meier Plotter databases. The associations of MKI67 with related gene marker sets and immune infiltration were inspected through TISIDB, GEPIA2, and TIMER. We chose MKI67 to analyse biological processes (BPs) and KEGG pathways related to the coexpressed genes. Furthermore, the gene–miRNA interaction network for MKI67 in liver cancer was also examined based on the miRWalk database. Results MKI67 expression decreased in many cancers related to the dismal prognostic outcome of LIHC. We found that MKI67 significantly affected the prognosis of LIHC in terms of histology and grade. Increased MKI67 levels were directly proportional to the increased immune infiltration degrees of numerous immune cells and functional T cells, such as exhausted T cells. In addition, several critical genes related to exhausted T cells, including TIM-3, TIGIT, PD-1, LAG3, and CXCL13, were strongly related to MKI67. Further analyses showed that MKI67 was associated with adaptive immunity, cell adhesion molecules (CAMs), and chemokine/immune response signal transduction pathways. Conclusion MKI67 acts as a prognostic prediction biomarker in several cancers, particularly LIHC. Upregulation of MKI67 elevates the degree of immune infiltration of many immune cell subtypes, including functional T cells, CD4+ T cells, and CD8+ T cells. Furthermore, MKI67 shows a close correlation with T cell exhaustion, which plays a vital role in promoting T cell exhaustion within LIHC. Detection of the MKI67 level contributes to prognosis prediction and MKI67 modulation within exhausted T cells, thus providing a new method to optimize the efficacy of anti-LIHC immunotherapy.Shi-yi WuPan LiaoLu-yu YanQian-yi ZhaoZhao-yu XieJie DongHong-tao SunBMCarticleImmunotherapyImmune infiltrationT cells exhaustionPrognosisMKI67Diseases of the digestive system. GastroenterologyRC799-869ENBMC Gastroenterology, Vol 21, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunotherapy Immune infiltration T cells exhaustion Prognosis MKI67 Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Immunotherapy Immune infiltration T cells exhaustion Prognosis MKI67 Diseases of the digestive system. Gastroenterology RC799-869 Shi-yi Wu Pan Liao Lu-yu Yan Qian-yi Zhao Zhao-yu Xie Jie Dong Hong-tao Sun Correlation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinoma
description	Abstract Background MKI67 plays a vital role in the tumour microenvironment (TME) and congenital immunity. The present work focuses on exploring the prognosis prediction performance of MKI67 and its associations with T cell activity and immune infiltration within numerous cancers, especially hepatocellular liver carcinoma (LIHC). Methods Oncomine, GEPIA2, and HPA were adopted to analyse MKI67 levels in different types of cancers. The prognostic prediction performance of MKI67 was evaluated through the TCGA portal, GEPIA2, LOGpc, and Kaplan–Meier Plotter databases. The associations of MKI67 with related gene marker sets and immune infiltration were inspected through TISIDB, GEPIA2, and TIMER. We chose MKI67 to analyse biological processes (BPs) and KEGG pathways related to the coexpressed genes. Furthermore, the gene–miRNA interaction network for MKI67 in liver cancer was also examined based on the miRWalk database. Results MKI67 expression decreased in many cancers related to the dismal prognostic outcome of LIHC. We found that MKI67 significantly affected the prognosis of LIHC in terms of histology and grade. Increased MKI67 levels were directly proportional to the increased immune infiltration degrees of numerous immune cells and functional T cells, such as exhausted T cells. In addition, several critical genes related to exhausted T cells, including TIM-3, TIGIT, PD-1, LAG3, and CXCL13, were strongly related to MKI67. Further analyses showed that MKI67 was associated with adaptive immunity, cell adhesion molecules (CAMs), and chemokine/immune response signal transduction pathways. Conclusion MKI67 acts as a prognostic prediction biomarker in several cancers, particularly LIHC. Upregulation of MKI67 elevates the degree of immune infiltration of many immune cell subtypes, including functional T cells, CD4+ T cells, and CD8+ T cells. Furthermore, MKI67 shows a close correlation with T cell exhaustion, which plays a vital role in promoting T cell exhaustion within LIHC. Detection of the MKI67 level contributes to prognosis prediction and MKI67 modulation within exhausted T cells, thus providing a new method to optimize the efficacy of anti-LIHC immunotherapy.
format	article
author	Shi-yi Wu Pan Liao Lu-yu Yan Qian-yi Zhao Zhao-yu Xie Jie Dong Hong-tao Sun
author_facet	Shi-yi Wu Pan Liao Lu-yu Yan Qian-yi Zhao Zhao-yu Xie Jie Dong Hong-tao Sun
author_sort	Shi-yi Wu
title	Correlation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinoma
title_short	Correlation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinoma
title_full	Correlation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinoma
title_fullStr	Correlation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinoma
title_full_unstemmed	Correlation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinoma
title_sort	correlation of mki67 with prognosis, immune infiltration, and t cell exhaustion in hepatocellular carcinoma
publisher	BMC
publishDate	2021
url	https://doaj.org/article/cc7537cd99fc4c1ba0a4be3217c384c9
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Correlation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinoma

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