Heat shock proteins (HSPs) are the evolutionary family of proteins that are highly conserved and present widely in various organisms and play an array of important roles and cellular functions. Currently, very few or no studies are based on the systematic analysis of the HSPs in Glioblastoma (GBMs) and ependymomas. We performed an integrated omics analysis to predict the mutual regulatory differential HSP signatures that were associated with both glioblastoma and ependymomas. Further, we explored the various common dysregulated biological processes operating in both the tumors, and were analyzed using functional enrichment, gene ontology along with the pathway analysis of the predicted HSPs. We established an interactome network of protein-protein interaction (PPIN) to identify the hub HSPs that were commonly associated with GBMs and ependymoma. To understand the mutual molecular mechanism of the HSPs in both malignancies, transcription factors, and miRNAs overlapping with both diseases were explored. Moreover, a transcription factor-miRNAs-HSPs coregulatory network was constructed along with the prediction of potential candidate drugs that were based on perturbation-induced gene expression analysis. Based on the RNA-sequencing data, HSP90AB1 was identified as the most promising target among other predicted HSPs. Finally, the ranking of the drugs was arranged based on various drug scores. In conclusion, this study gave a spotlight on the mutual targetable HSPs, biological pathways, and regulatory signatures associated with GBMs and ependymoma with an improved understanding of crosstalk involved. Additionally, the role of therapeutics was also explored against HSP90AB1. These findings could potentially be able to explain the interplay of HSP90AB1 and other HSPs within these two malignancies.

热休克蛋白（HSP）是高度保守的蛋白质进化家族，广泛存在于各种生物体中，发挥着一系列重要作用和细胞功能。目前，很少或没有研究基于胶质母细胞瘤（GBM）和室管膜瘤中 HSP 的系统分析。我们进行了综合组学分析，以预测与胶质母细胞瘤和室管膜瘤相关的相互调节差异 HSP 特征。此外，我们探索了两种肿瘤中各种常见的失调生物过程，并使用功能富集、基因本体论以及预测的 HSP 的通路分析进行了分析。我们建立了蛋白质-蛋白质相互作用 (PPIN) 的相互作用组网络，以识别通常与 GBM 和室管膜瘤相关的中枢 HSP。为了了解两种恶性肿瘤中 HSP 的相互分子机制，我们探索了与两种疾病重叠的转录因子和miRNA 。此外，还构建了转录因子-miRNA-HSPs共调节网络以及基于扰动诱导的基因表达分析的潜在候选药物的预测。根据 RNA 测序数据，HSP90AB1 被确定为其他预测的 HSP 中最有希望的靶标。最后根据各种药品评分对药品进行排名。总之，这项研究重点关注了与 GBM 和室管膜瘤相关的相互可靶向的 HSP、生物途径和调控特征，并加深了对所涉及串扰的理解。此外，还探讨了针对 HSP90AB1 的疗法的作用。这些发现可能能够解释 HSP90AB1 和其他 HSP 在这两种恶性肿瘤中的相互作用。