开发和验证HSP90AA1作为HIF-1α通路相关肝细胞癌预后特征中的风险基因
Development and validation of HSP90AA1 as a risk gene in a HIF-1α pathway-related prognostic signature for hepatocellular carcinoma.
摘要(中文译文)
肝细胞癌（HCC）是一种常见的恶性肿瘤，其发病率和死亡率在全球范围内呈上升趋势。确定一个稳健的预后特征仍是HCC治疗中尚未满足的临床需求。本研究从癌症基因组图谱（TCGA）数据库中获取HCC患者的转录组和临床数据，并从GeneCards中筛选出前100个HIF-1α通路相关基因（HPRGs）。采用单因素Cox回归、LASSO正则化Cox回归和多因素Cox回归，建立了一个四基因预后特征（HSP90AA1、ANGPT2、NPM1和LDHA）。通过受试者工作特征（ROC）曲线分析、一致性指数（C-index）和决策曲线分析（DCA）验证了其稳健的预测性能。随后，根据风险评分中位数将HCC患者分为高-risk和低-risk组，生存分析证实高-risk组患者的预后明显较差。此外，特征基因的表达水平与风险评分呈正相关，并在GSE121248和GSE14520数据集中高-risk HCC组织中过表达。此外，药物敏感性分析表明，高-risk组对5-氟尿嘧啶、吉西他滨、紫杉醇、索拉非尼和舒尼替尼表现出更高的敏感性。孟德尔随机化（MR）和贝叶斯共定位分析验证了HSP90AA1和LDHA作为潜在的可成药靶点。此外，功能验证实验表明，敲低HSP90AA1可抑制HCC细胞的增殖、迁移和侵袭。总体而言，本研究提出了一种新的HCC预后特征，并强调了HSP90AA1作为生物标志物和治疗靶点的潜力。
Abstract
Hepatocellular carcinoma (HCC) is a prevalent malignancy with globally increasing incidence and mortality rates. The identification of a robust prognostic signature remains an unmet clinical need in HCC treatment. In this study, transcriptome and clinical data of HCC patients were retrieved from The Cancer Genome Atlas (TCGA) database, and the top 100 HIF-1α pathway-related genes (HPRGs) were selected from GeneCards. Using univariate Cox regression, LASSO-regularized Cox regression, and multivariate Cox regression, a four-gene prognostic signature (HSP90AA1, ANGPT2, NPM1 and LDHA) was established. Its robust predictive performance was validated using receiver operating characteristic (ROC) curve analysis, the concordance index (C-index), and decision curve analysis (DCA). Subsequently, HCC patients were stratified into high- and low-risk groups according to the median risk score, and survival analysis confirmed markedly inferior prognosis for patients in the high-risk group. Furthermore, the expression level of the signature genes correlated positively with risk score and were overexpressed in high-risk HCC tissues in the GSE121248 and GSE14520 datasets. Besides, the drug sensitivity analysis demonstrated that the high-risk group exhibited greater sensitivity to 5-fluorouracil, gemcitabine, paclitaxel, sorafenib, and sunitinib. Mendelian randomization (MR) and Bayesian colocalization analyses validated HSP90AA1 and LDHA as potential druggable targets. Furthermore, functional validation experiments demonstrated that knockdown of HSP90AA1 could impede the proliferation, migration, and invasion of HCC cells. Overall, this research presents a novel prognostic signature for HCC and highlights the potential of HSP90AA1 as a biomarker and therapeutic target.
如何引用
AMA
Yanyan Zhang, Hantao Huang, Qimin Su, Yan Zhou, Xinyan Li, Kunwei Peng, et al. Development and validation of HSP90AA1 as a risk gene in a HIF-1α pathway-related prognostic signature for hepatocellular carcinoma.. Biochemical and biophysical research communications. 2026; doi:10.1016/j.bbrc.2026.154239.
APA
Yanyan Zhang, Hantao Huang, Qimin Su, Yan Zhou, Xinyan Li, Kunwei Peng, et al (2026). Development and validation of HSP90AA1 as a risk gene in a HIF-1α pathway-related prognostic signature for hepatocellular carcinoma.. Biochemical and biophysical research communications. https://doi.org/10.1016/j.bbrc.2026.154239
GB/T 7714
Yanyan Zhang, Hantao Huang, Qimin Su, Yan Zhou, Xinyan Li, Kunwei Peng, et al. Development and validation of HSP90AA1 as a risk gene in a HIF-1α pathway-related prognostic signature for hepatocellular carcinoma.[J]. Biochemical and biophysical research communications, 2026 doi:10.1016/j.bbrc.2026.154239.
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