BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

Background: BTBD10 serves as an activator of Akt family members through decreasing the protein phosphatase 2A-mediated dephosphorylation. The present study attempted to investigate the prognostic value of BTBD10 in hepatocellular carcinoma (HCC), specially, its relationship with tumor-infiltrating l...

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Main Authors: Jianhui Li, Xiaojuan Tian, Ye Nie, Ying He, Wenlong Wu, Xinjun Lei, Tianchen Zhang, Yanfang Wang, Zhenzhen Mao, Hong Zhang, Xuan Zhang, Wenjie Song
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2021.762541/full
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author Jianhui Li
Jianhui Li
Xiaojuan Tian
Ye Nie
Ye Nie
Ying He
Wenlong Wu
Xinjun Lei
Tianchen Zhang
Yanfang Wang
Zhenzhen Mao
Hong Zhang
Xuan Zhang
Wenjie Song
author_facet Jianhui Li
Jianhui Li
Xiaojuan Tian
Ye Nie
Ye Nie
Ying He
Wenlong Wu
Xinjun Lei
Tianchen Zhang
Yanfang Wang
Zhenzhen Mao
Hong Zhang
Xuan Zhang
Wenjie Song
author_sort Jianhui Li
collection DOAJ
description Background: BTBD10 serves as an activator of Akt family members through decreasing the protein phosphatase 2A-mediated dephosphorylation. The present study attempted to investigate the prognostic value of BTBD10 in hepatocellular carcinoma (HCC), specially, its relationship with tumor-infiltrating lymphocytes (TILs).Methods: BTBD10 expression was evaluated in HCC using The Cancer Genome Atlas (TCGA) and Xijing Hospital database, and verified in HCC cell lines. Cox analyses were performed to analyze independent prognostic risk factors for HCC. The optimal cut-off value of BTBD10 was calculated, by which all patients were divided into two groups to compare the overall survival (OS). The signaling pathways were predicted, by which BTBD10 may affect the progression of HCC. To investigate the impact of BTBD10 on HCC immunotherapy, correlations between BTBD10 and TILs, immune checkpoints, m6A methylation-related genes and ferroptosis-related genes were assessed. The distribution of half-maximal inhibitory concentration (IC50) of diverse targeted drugs was observed based on the differential expression of BTBD10.Results: BTBD10 expression was higher in HCC tissues and cell lines than that of normal liver tissues and cells. The patients with high expression of BTBD10 showed a worse OS, as compared to that of BTBD10 low-expressing group. Cox analyses indicated that BTBD10 was an independent prognostic risk factor for HCC. Several molecular pathways of immune responses were activated in HCC patients with high-expressing of BTBD10. Furthermore, BTBD10 expression was demonstrated to be positively correlated with tumor-infiltrating B cells, T cells, macrophages, neutrophils and dendritic cells. Meanwhile, the expression of BTBD10 was synchronized with that of several m6A methylation-related genes, ferroptosis-related genes and immune checkpoints. The IC50 scores of Sorafenib, Navitoclax, Veliparib, Luminespib, and Imatinib were found to be lower in BTBD10 high-expressing HCC group.Conclusion: BTBD10 negatively regulates tumor immunity in HCC and exhibits adverse effect on the prognosis of HCC, which could be a potential target for immunotherapy.
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spelling doaj.art-1c7d7886d37047978be584d913261f862022-12-21T19:24:15ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-01-01810.3389/fmolb.2021.762541762541BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular CarcinomaJianhui Li0Jianhui Li1Xiaojuan Tian2Ye Nie3Ye Nie4Ying He5Wenlong Wu6Xinjun Lei7Tianchen Zhang8Yanfang Wang9Zhenzhen Mao10Hong Zhang11Xuan Zhang12Wenjie Song13Xi’an Medical University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaOperating Room, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaXi’an Medical University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaXi’an Medical University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaXi’an Medical University, Xi’an, ChinaXi’an Medical University, Xi’an, ChinaXi’an Medical University, Xi’an, ChinaXi’an Medical University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaBackground: BTBD10 serves as an activator of Akt family members through decreasing the protein phosphatase 2A-mediated dephosphorylation. The present study attempted to investigate the prognostic value of BTBD10 in hepatocellular carcinoma (HCC), specially, its relationship with tumor-infiltrating lymphocytes (TILs).Methods: BTBD10 expression was evaluated in HCC using The Cancer Genome Atlas (TCGA) and Xijing Hospital database, and verified in HCC cell lines. Cox analyses were performed to analyze independent prognostic risk factors for HCC. The optimal cut-off value of BTBD10 was calculated, by which all patients were divided into two groups to compare the overall survival (OS). The signaling pathways were predicted, by which BTBD10 may affect the progression of HCC. To investigate the impact of BTBD10 on HCC immunotherapy, correlations between BTBD10 and TILs, immune checkpoints, m6A methylation-related genes and ferroptosis-related genes were assessed. The distribution of half-maximal inhibitory concentration (IC50) of diverse targeted drugs was observed based on the differential expression of BTBD10.Results: BTBD10 expression was higher in HCC tissues and cell lines than that of normal liver tissues and cells. The patients with high expression of BTBD10 showed a worse OS, as compared to that of BTBD10 low-expressing group. Cox analyses indicated that BTBD10 was an independent prognostic risk factor for HCC. Several molecular pathways of immune responses were activated in HCC patients with high-expressing of BTBD10. Furthermore, BTBD10 expression was demonstrated to be positively correlated with tumor-infiltrating B cells, T cells, macrophages, neutrophils and dendritic cells. Meanwhile, the expression of BTBD10 was synchronized with that of several m6A methylation-related genes, ferroptosis-related genes and immune checkpoints. The IC50 scores of Sorafenib, Navitoclax, Veliparib, Luminespib, and Imatinib were found to be lower in BTBD10 high-expressing HCC group.Conclusion: BTBD10 negatively regulates tumor immunity in HCC and exhibits adverse effect on the prognosis of HCC, which could be a potential target for immunotherapy.https://www.frontiersin.org/articles/10.3389/fmolb.2021.762541/fullBTBD10hepatocellular carcinomaprognosisbiomarkerimmune infiltration
spellingShingle Jianhui Li
Jianhui Li
Xiaojuan Tian
Ye Nie
Ye Nie
Ying He
Wenlong Wu
Xinjun Lei
Tianchen Zhang
Yanfang Wang
Zhenzhen Mao
Hong Zhang
Xuan Zhang
Wenjie Song
BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma
Frontiers in Molecular Biosciences
BTBD10
hepatocellular carcinoma
prognosis
biomarker
immune infiltration
title BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma
title_full BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma
title_fullStr BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma
title_full_unstemmed BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma
title_short BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma
title_sort btbd10 is a prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma
topic BTBD10
hepatocellular carcinoma
prognosis
biomarker
immune infiltration
url https://www.frontiersin.org/articles/10.3389/fmolb.2021.762541/full
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