Heat Shock Protein Beta 1 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Hepatocellular Carcinoma

Abstract

Background Hepatocellular carcinoma (HCC) is one of the most serious malignancies. The main features of HCC are vascular invasion and drug resistance. Ferroptosis is a novel cell program that is involved in several diseases, such as cancer. Heat shock protein beta 1 (HSPB1) is a major component of heat shock proteins. A recent study showed that HSPB1 could be a new therapeutic target for colorectal cancer with 5-fluorouracil-acquired resistance. However, the functional role of HSPB1 in HCC remains unclear. Aim The aim of this study is to clarify HSPB1 expression in HCC and its potential therapeutic and prognostic value. Methods We collected data on HSPB1 expression levels in HCC and normal liver tissues from The Cancer Genome Atlas and Gene Expression Omnibus databases. We then validated it using immunohistochemistry (IHC). Receiver operating characteristic and Kaplan–Meier survival curves were used to investigate the role of HSPB1 in the prognosis analysis of HCC. Further, we used the online Search Tool for the Retrieval of Interacting Genes/Proteins website, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes to conduct enrichment analysis and identify the predictive signaling pathways. Meanwhile, we used the TIMER and GSVA package of R (v3.6.3) to analyze the association between HSPB1 and immunocyte infiltration. Results Compared to normal tissues, there was differential expression of HSPB1 in pan-cancers. HSPB1 expression was higher in HCC tissues than in normal tissues ( p <0.05). There was an evident significant difference between HSPB1 mRNA levels and histologic grade, vascular invasion, and alpha-fetoprotein level (all p values<0.05). Univariate analysis indicated that HCC patients with high HSPB1 levels had shorter overall survival rates than those with low HSPB1 levels ( p <0.05). MAPK14, HSPA8, MAPKAPK3, MAPKAPK5, and MAPKAPK2 are essential proteins that interact with HSPB1. There was a significant correlation between HSPB1 expression levels and immune cell infiltration, including CD4 + T cells ( r =0.203, p <0.05). Conclusion High HSPB1 expression is closely associated with a worse prognosis in HCC patients, and HSPB1 may be a target of immunotherapy in HCC.

Iron Oxide Nanoparticles Functionalized with Fucoidan: a Potential Theranostic Nanotool for Hepatocellular Carcinoma

“…Interestingly, many previous studies have revealed that high expression of HSP70 and HSP90 is associated to tumor development and tumor aggressiveness [45,46] . Moreover, the level of HSPbeta1, a major component of HSPs, and HSC71, were shown to be higher in hepatocellular carcinoma (HCC) tissues than in normal liver tissue [47,48] . As a result, downregulation of HSPs, suggest an anti‐cancer effect of the USPIO‐fucoidan‐NPs and free fucoidan in Huh‐7 cells.…”

“…[45,46] Moreover, the level of HSPbeta1, a major component of HSPs, and HSC71, were shown to be higher in hepatocellular carcinoma (HCC) tissues than in normal liver tissue. [47,48] As a result, downregulation of HSPs, suggest an anticancer effect of the USPIO-fucoidan-NPs and free fucoidan in Huh-7 cells. In addition, the decrease in abundance of HSP70 and HSP90 could result from the reduction of the ROS production in treated Huh-7 cells (Figure 4).…”

The Critical Role of Ferroptosis in Hepatocellular Carcinoma

“…HCC patients with high HSPB1 levels showed worse overall survival rates and poor prognosis. Overexpression of HSPB1 was closely correlated with migration and invasion of HCC cells, as well as the in vivo metastasis ( Zhang et al, 2016 ; Long et al, 2021 ). Besides, HSPB1 was identified as a hub gene in the regulatory network associated with HCC progression and ferroptosis ( Fei et al, 2021 ).…”

Single-cell metabolic profiling reveals subgroups of primary human hepatocytes showing heterogeneous responses to drug challenge

“…For example, CYP4A11, involved in NAFLD progression by inducing ROS-related lipid peroxidation and inflammation [93][94][95], was significantly up-regulated in subgroups II and III; and CIDEC, a promotor of triglyceride accumulation [96,97], was significantly up-regulated in subgroups I, II and III. Cells losing expression (IV), upregulated LGALS1 [98,99], and HSPB1 [100,101] (Figure 3D and Supp. Figure 5D), which are known markers in the gene ontology pathway GO:0006950: "response to stress".…”