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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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | BMC Gastroenterology |
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| Online Access: | https://doi.org/10.1186/s12876-021-01984-2 |
| _version_ | 1818922177768980480 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T01:49:24Z |
| format | Article |
| id | doaj.art-cc7537cd99fc4c1ba0a4be3217c384c9 |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-12-20T01:49:24Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj.art-cc7537cd99fc4c1ba0a4be3217c384c92022-12-21T19:57:41ZengBMCBMC Gastroenterology1471-230X2021-11-0121111910.1186/s12876-021-01984-2Correlation of MKI67 with prognosis, immune infiltration, and T cell exhaustion in hepatocellular carcinomaShi-yi Wu0Pan Liao1Lu-yu Yan2Qian-yi Zhao3Zhao-yu Xie4Jie Dong5Hong-tao Sun6Department of Cardiology, Inner Mongolia Forestry General HospitalDepartment of Neurology, Inner Mongolia Forestry General HospitalDepartment of Cardiology, Inner Mongolia Forestry General HospitalDepartment of Cardiology, Inner Mongolia Forestry General HospitalOphthalmology Department, The Second Xiangya Hospital, Central South UniversityDepartment of Gastroenterology, Inner Mongolia Forestry General HospitalDepartment of Cardiology, Affiliated Hospital of Inner Mongolia University for NationalitiesAbstract 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.https://doi.org/10.1186/s12876-021-01984-2ImmunotherapyImmune infiltrationT cells exhaustionPrognosisMKI67 |
| spellingShingle | 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 BMC Gastroenterology Immunotherapy Immune infiltration T cells exhaustion Prognosis MKI67 |
| title | 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_short | 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 |
| topic | Immunotherapy Immune infiltration T cells exhaustion Prognosis MKI67 |
| url | https://doi.org/10.1186/s12876-021-01984-2 |
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