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

Jianhui Li; Xiaojuan Tian; Ye Nie; Ying He; Wenlong Wu; Xinjun Lei; Tianchen Zhang; Yanfang Wang; Zhenzhen Mao; Hong Zhang; Xuan Zhang; Wenjie Song

doi:10.3389/fmolb.2021.762541

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

Front Mol Biosci. 2022 Jan 4:8:762541. doi: 10.3389/fmolb.2021.762541. eCollection 2021.

Authors

Jianhui Li^{1

2}, Xiaojuan Tian³, Ye Nie^{1

2}, Ying He¹, Wenlong Wu², Xinjun Lei¹, Tianchen Zhang¹, Yanfang Wang¹, Zhenzhen Mao¹, Hong Zhang², Xuan Zhang², Wenjie Song²

Affiliations

¹ Xi'an Medical University, Xi'an, China.
² Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
³ Operating Room, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Abstract

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.

Keywords: BTBD10; biomarker; hepatocellular carcinoma; immune infiltration; prognosis.