Cargando…
Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma
Methyltransferase-like 18 (METTL18), a METTL family member, is abundant in hepatocellular carcinoma (HCC). Studies have indicated the METTL family could regulate the progress of diverse malignancies while the role of METTL18 in HCC remains unclear. Data of HCC patients were acquired from the cancer...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187872/ https://www.ncbi.nlm.nih.gov/pubmed/34123827 http://dx.doi.org/10.3389/fonc.2021.665192 |
_version_ | 1783705224399028224 |
---|---|
author | Li, Tian-Hao Qin, Cheng Zhao, Bang-Bo Cao, Hong-Tao Yang, Xiao-Ying Wang, Yuan-Yang Li, Ze-Ru Zhou, Xing-Tong Wang, Wei-Bin |
author_facet | Li, Tian-Hao Qin, Cheng Zhao, Bang-Bo Cao, Hong-Tao Yang, Xiao-Ying Wang, Yuan-Yang Li, Ze-Ru Zhou, Xing-Tong Wang, Wei-Bin |
author_sort | Li, Tian-Hao |
collection | PubMed |
description | Methyltransferase-like 18 (METTL18), a METTL family member, is abundant in hepatocellular carcinoma (HCC). Studies have indicated the METTL family could regulate the progress of diverse malignancies while the role of METTL18 in HCC remains unclear. Data of HCC patients were acquired from the cancer genome atlas (TCGA) and gene expression omnibus (GEO). The expression level of METTL18 in HCC patients was compared with normal liver tissues by Wilcoxon test. Then, the logistic analysis was used to estimate the correlation between METTL18 and clinicopathological factors. Besides, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and single-sample Gene Set Enrichment Analysis (ssGSEA) were used to explore relevant functions and quantify the degree of immune infiltration for METTL18. Univariate and Multivariate Cox analyses and Kaplan–Meier analysis were used to estimate the association between METTL18 and prognosis. Besides, by cox multivariate analysis, a nomogram was conducted to forecast the influence of METTL18 on survival rates. METTL18-high was associated with Histologic grade, T stage, Pathologic stage, BMI, Adjacent hepatic tissue inflammation, AFP, Vascular invasion, and TP53 status (P < 0.05). HCC patients with METTL18-high had a poor Overall-Survival [OS; hazard ratio (HR): 1.87, P < 0.001), Disease-Specific Survival (DSS, HR: 1.76, P = 0.015), and Progression-Free Interval (PFI, HR: 1.51, P = 0.006). Multivariate analysis demonstrated that METTL18 was an independent factor for OS (HR: 2.093, P < 0.001), DSS (HR: 2.404, P = 0.015), and PFI (HR: 1.133, P = 0.006). Based on multivariate analysis, the calibration plots and C-indexes of nomograms showed an efficacious predictive effect for HCC patients. GSEA demonstrated that METTL18-high could activate G2M checkpoint, E2F targets, KRAS signaling pathway, and Mitotic Spindle. There was a positive association between the METTL18 and abundance of innate immunocytes (T helper 2 cells) and a negative relation to the abundance of adaptive immunocytes (Dendritic cells, Cytotoxic cells etc.). Finally, we uncovered knockdown of METTL18 significantly suppressed the proliferation, invasion, and migration of HCC cells in vitro. This research indicates that METTL18 could be a novel biomarker to evaluate HCC patients’ prognosis and an important regulator of immune responses in HCC. |
format | Online Article Text |
id | pubmed-8187872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81878722021-06-10 Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma Li, Tian-Hao Qin, Cheng Zhao, Bang-Bo Cao, Hong-Tao Yang, Xiao-Ying Wang, Yuan-Yang Li, Ze-Ru Zhou, Xing-Tong Wang, Wei-Bin Front Oncol Oncology Methyltransferase-like 18 (METTL18), a METTL family member, is abundant in hepatocellular carcinoma (HCC). Studies have indicated the METTL family could regulate the progress of diverse malignancies while the role of METTL18 in HCC remains unclear. Data of HCC patients were acquired from the cancer genome atlas (TCGA) and gene expression omnibus (GEO). The expression level of METTL18 in HCC patients was compared with normal liver tissues by Wilcoxon test. Then, the logistic analysis was used to estimate the correlation between METTL18 and clinicopathological factors. Besides, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and single-sample Gene Set Enrichment Analysis (ssGSEA) were used to explore relevant functions and quantify the degree of immune infiltration for METTL18. Univariate and Multivariate Cox analyses and Kaplan–Meier analysis were used to estimate the association between METTL18 and prognosis. Besides, by cox multivariate analysis, a nomogram was conducted to forecast the influence of METTL18 on survival rates. METTL18-high was associated with Histologic grade, T stage, Pathologic stage, BMI, Adjacent hepatic tissue inflammation, AFP, Vascular invasion, and TP53 status (P < 0.05). HCC patients with METTL18-high had a poor Overall-Survival [OS; hazard ratio (HR): 1.87, P < 0.001), Disease-Specific Survival (DSS, HR: 1.76, P = 0.015), and Progression-Free Interval (PFI, HR: 1.51, P = 0.006). Multivariate analysis demonstrated that METTL18 was an independent factor for OS (HR: 2.093, P < 0.001), DSS (HR: 2.404, P = 0.015), and PFI (HR: 1.133, P = 0.006). Based on multivariate analysis, the calibration plots and C-indexes of nomograms showed an efficacious predictive effect for HCC patients. GSEA demonstrated that METTL18-high could activate G2M checkpoint, E2F targets, KRAS signaling pathway, and Mitotic Spindle. There was a positive association between the METTL18 and abundance of innate immunocytes (T helper 2 cells) and a negative relation to the abundance of adaptive immunocytes (Dendritic cells, Cytotoxic cells etc.). Finally, we uncovered knockdown of METTL18 significantly suppressed the proliferation, invasion, and migration of HCC cells in vitro. This research indicates that METTL18 could be a novel biomarker to evaluate HCC patients’ prognosis and an important regulator of immune responses in HCC. Frontiers Media S.A. 2021-05-26 /pmc/articles/PMC8187872/ /pubmed/34123827 http://dx.doi.org/10.3389/fonc.2021.665192 Text en Copyright © 2021 Li, Qin, Zhao, Cao, Yang, Wang, Li, Zhou and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Li, Tian-Hao Qin, Cheng Zhao, Bang-Bo Cao, Hong-Tao Yang, Xiao-Ying Wang, Yuan-Yang Li, Ze-Ru Zhou, Xing-Tong Wang, Wei-Bin Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma |
title | Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma |
title_full | Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma |
title_fullStr | Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma |
title_full_unstemmed | Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma |
title_short | Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma |
title_sort | identification mettl18 as a potential prognosis biomarker and associated with immune infiltrates in hepatocellular carcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187872/ https://www.ncbi.nlm.nih.gov/pubmed/34123827 http://dx.doi.org/10.3389/fonc.2021.665192 |
work_keys_str_mv | AT litianhao identificationmettl18asapotentialprognosisbiomarkerandassociatedwithimmuneinfiltratesinhepatocellularcarcinoma AT qincheng identificationmettl18asapotentialprognosisbiomarkerandassociatedwithimmuneinfiltratesinhepatocellularcarcinoma AT zhaobangbo identificationmettl18asapotentialprognosisbiomarkerandassociatedwithimmuneinfiltratesinhepatocellularcarcinoma AT caohongtao identificationmettl18asapotentialprognosisbiomarkerandassociatedwithimmuneinfiltratesinhepatocellularcarcinoma AT yangxiaoying identificationmettl18asapotentialprognosisbiomarkerandassociatedwithimmuneinfiltratesinhepatocellularcarcinoma AT wangyuanyang identificationmettl18asapotentialprognosisbiomarkerandassociatedwithimmuneinfiltratesinhepatocellularcarcinoma AT lizeru identificationmettl18asapotentialprognosisbiomarkerandassociatedwithimmuneinfiltratesinhepatocellularcarcinoma AT zhouxingtong identificationmettl18asapotentialprognosisbiomarkerandassociatedwithimmuneinfiltratesinhepatocellularcarcinoma AT wangweibin identificationmettl18asapotentialprognosisbiomarkerandassociatedwithimmuneinfiltratesinhepatocellularcarcinoma |