Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target
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Published:2024-01-20
Issue:1
Volume:23
Page:
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ISSN:1476-4598
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Container-title:Molecular Cancer
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language:en
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Short-container-title:Mol Cancer
Author:
Huang Xiaoliang,Zhang Weiming,Yang Na,Zhang Yujie,Qin Tianyu,Ruan Hanyi,Zhang Yan,Tian Chao,Mo Xianwei,Tang Weizhong,Liu Jungang,Zhang Beibei
Abstract
AbstractHeat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future.
Funder
Guangxi Medical and Health Appropriate Technology Development and Promotion Application Project Project of the Department of Education of Guangxi Zhuang Autonomous Region to improve the basic research ability of young and middle-aged teachers Guangxi Natural Science Foundation National Natural Science Foundation of China Yunnan Natural Science Foundation Yunan University Research Foundation
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Medicine
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