Analysis of the prognostic, diagnostic and immunological role of HSP90α in malignant tumors

Abstract

Heat shock protein 90α (HSP90α) encoded by the HSP90AA1 gene, is the stress inducible isoform of the molecular chaperone HSP90, and was demonstrated as a promising hallmark to diagnose, prognosis in malignant tumors. This study is to evaluate the value of HSP90α in diagnosis, prognosis and immunotherapy of malignant tumors by investigating the expression of HSP90α in plasma of various tumors and analyzing the expression of HSP90α at gene and protein levels via pan-cancer database. We founded that levels of HSP90α in malignant tumors groups were significantly higher than healthy controls in serum. Pan-cancer analysis showed that HSP90AA1 was highly expressed in 27 of 33 tumors, but low in individual cancers (such as renal malignancies). The plasma HSP90α level was positively correlated with the stage of malignant tumor, but there was no significant difference between HSP90AA1 and the stage of most tumors. Cox regression analysis showed that HSP90AA1 expression was significantly correlated with OS in only 6 of the 32 cancers, including LIHC, KIRC, HNSC, LUAD, BRCA and MESO. Up-regulation of HSP90AA1 in most tumors was positively correlated with PDCD1LG2 and CD274 immune checkpoint genes. T cell CD8+ was positively correlated with HSP90AA1 in COAD, DLBC and UVM, and negatively correlated with HSP90AA1 in ESCA, GBM, HNSC, KIRC, KIRP, UCEC and STAD. The AUC of HSP90α are generally high in different tumor groups, which indicated its diagnostic value in malignant tumors. In conclusion, serum HSP90α in patients with malignant tumor is generally elevated, which is of positive significance as an independent diagnosis and combined diagnosis. However, we found that the expression level of HSP90AA1 gene in most tumors was not completely consistent with the serum level, and even down-regulated in some tumors. Plasma levels can be used as biomarkers of poor prognosis in some tumors, but it cannot be used as a biomarker for poor prognosis of all tumors, and more in-depth studies are needed.

Calibrated Identification of Feature Dependencies in Single-cell Multiomics

“…Our approach provided a significant number of genes related to T cell function in the tumor microenvironment, including HSP90AA1, ETS1, CXCR4, RGS1, and FYN, all detected at the gene level. HSP90AA1, for instance, encodes a heat shock protein, whose overexpression correlates with tumor progression and a poor prognosis in NSCLC [53, 54], and has been shown to correlate with an exhausted phenotype of CD8 T cells in tumors [55]. CXCR4 encodes a chemokine receptor whose expression is associated with the formation of lymphoid follicles that we detected outside of the tumor [56].…”

Network Pharmacology and Bioinformatics Analysis to Identify the Molecular Targets and its Biological Mechanisms of Sciadopitysin against Glioblastoma

“…Overexpression of HSP90 is strongly associated with various cancers; for example, in breast cancer, the expression level of HSP90 is closely related to the survival of patients, and the abnormally high expression level of HSP90 reflects the poor treatment effect [16][17][18]. HSP90 is a promising marker for the diagnosis and prognosis of malignant tumors [14,19]. In glioblastoma, the expression of HSP90α was abnormally high [20,21].…”

A comprehensive prognostic score for head and neck squamous cancer driver genes and phenotype traits

“…Among the 6 signature genes, CRLF2 as part of an immune score-related risk signature, performed well in the prognostic stratification of OSCC patients and could effectively distinguish their survival status [ 44 ]. HSP90AA1 was highly expressed in various tumors and significantly correlated with poor prognosis [ 45 ]. HSP90AA1/IL-17 signaling pathway was associated with cisplatin resistance in head and neck squamous carcinoma [ 46 ].…”