Huang Tianyi, Xu Shimeng, Li Ming, Lu Cuihua, Zhang Jiaying
Department Gastroenterology, Medical School of Nantong University, Affiliated Hospital of Nantong University, Nantong, 226001, China.
Emergency department, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, SuzhouDushu Lake Hospital, Suzhou, 215123, China.
Sci Rep. 2025 Aug 24;15(1):31151. doi: 10.1038/s41598-025-16843-3.
Heat shock proteins (HSPs) are evolutionarily conserved molecular chaperones that maintain cellular proteostasis under physiological and stress conditions. HSPH1 (Heat Shock Protein Family H Member 1, also known as HSP105 or HSP110) belongs to the HSP110 family and functions as a nucleotide exchange factor for HSP70, enhancing its folding activity. Beyond its canonical role, HSPH1 is increasingly recognized for its involvement in tumor progression. It has been reported to regulate cell proliferation, invasion, metastasis, and resistance to therapy in several cancers, including breast, lung, and liver cancer. Pan-cancer transcriptomic analyses have identified HSPH1 as frequently overexpressed and correlated with poor prognosis. In hepatocellular carcinoma (HCC), while other HSPs such as HSP70 and HSP90 are well-studied, the biological role of HSPH1 remains unclear. In this study, we systematically analyzed HSPH1 expression in HCC using TCGA and GEO datasets, and validated its clinical relevance in patient samples. HSPH1 was significantly upregulated in HCC tissues and associated with advanced tumor stage and worse overall survival. Functional enrichment and immune infiltration analyses suggested that HSPH1 participates in oncogenic pathways (e.g., p53, cell cycle) and modulates the tumor immune microenvironment. Knockdown of HSPH1 in HCC cell lines inhibited proliferation and colony formation. Together, our findings highlight HSPH1 as a potential prognostic biomarker and therapeutic target in HCC.
热休克蛋白（HSPs）是进化上保守的分子伴侣，在生理和应激条件下维持细胞蛋白质稳态。HSPH1（热休克蛋白家族H成员1，也称为HSP105或HSP110）属于HSP110家族，作为HSP70的核苷酸交换因子发挥作用，增强其折叠活性。除了其经典作用外，HSPH1在肿瘤进展中的作用越来越受到认可。据报道，它在包括乳腺癌、肺癌和肝癌在内的几种癌症中调节细胞增殖、侵袭、转移和对治疗的抗性。泛癌转录组分析已确定HSPH1经常过度表达并与不良预后相关。在肝细胞癌（HCC）中，虽然其他热休克蛋白如HSP70和HSP90已得到充分研究，但HSPH1的生物学作用仍不清楚。在本研究中，我们使用TCGA和GEO数据集系统分析了HSPH1在HCC中的表达，并在患者样本中验证了其临床相关性。HSPH1在HCC组织中显著上调，并与晚期肿瘤分期和较差的总生存期相关。功能富集和免疫浸润分析表明，HSPH1参与致癌途径（如p53、细胞周期）并调节肿瘤免疫微环境。在HCC细胞系中敲低HSPH1可抑制增殖和集落形成。总之，我们的研究结果突出了HSPH1作为HCC潜在的预后生物标志物和治疗靶点。
