Gao Xixi, Zhang Yingqing, Zhang Ming, Sun Yuejiao
Department of Respiratory, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.
Front Genet. 2024 Nov 22;15:1475511. doi: 10.3389/fgene.2024.1475511. eCollection 2024.
Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer (NSCLC), characterized by poor prognosis and a high mortality rate. Identifying reliable prognostic biomarkers and potential therapeutic targets is crucial for improving patient outcomes.
We conducted a comprehensive analysis of HJURP expression in LUAD using data from four cohorts: TCGA-LUAD (n = 453), GSE31210 (n = 226), GSE68465 (n = 442), and GSE72094 (n = 386). Univariate Cox regression analysis was employed to identify prognostic genes, with Kaplan-Meier survival analysis used to assess the predictive power of HJURP. Functional enrichment analyses were performed using MetaScape and FGSEA, and spatial transcriptomics and single-cell sequencing data were analyzed to explore HJURP's distribution and potential functions. Additionally, correlations between HJURP expression and genetic alterations, immune cell infiltration, and potential therapeutic responses were evaluated.
HJURP was identified as a significant prognostic biomarker in all four cohorts, with high expression associated with increased risk of overall survival (OS) death (TCGA-LUAD: HR = 1.93, 95% CI: 1.321-2.815, < 0.001; GSE31210: HR = 2.75, 95% CI: 1.319-5.735, = 0.007; GSE68465: HR = 1.57, 95% CI: 1.215-2.038, < 0.001; GSE72094: HR = 2.2, 95% CI: 1.485-3.27, < 0.001). Functional analyses indicated that HJURP is involved in DNA metabolic processes, cell cycle regulation, and mitotic processes, with significant activation of pathways related to MYC targets, G2M checkpoint, and DNA repair. High HJURP expression was associated with higher mutation frequencies in TP53, CSMD3, TTN, and MUC16, and positively correlated with pro-inflammatory immune cell infiltration and several immune checkpoints, including PD-L1 and PD-L2. Chemotherapeutic agents such as gefitinib and sorafenib were predicted to be effective against high HJURP-expressing tumors.
HJURP is a pivotal biomarker for LUAD, consistently associated with poor prognosis and advanced disease stages. Its high expression correlates with specific genetic alterations and immune profiles, highlighting its potential as a therapeutic target. Future studies should validate these findings in larger cohorts.
肺腺癌（LUAD）是非小细胞肺癌（NSCLC）最常见的亚型，预后较差且死亡率高。确定可靠的预后生物标志物和潜在的治疗靶点对于改善患者预后至关重要。
我们使用来自四个队列的数据对LUAD中HJURP的表达进行了全面分析：TCGA-LUAD（n = 453）、GSE31210（n = 226）、GSE68465（n = 442）和GSE72094（n = 386）。采用单变量Cox回归分析来确定预后基因，用Kaplan-Meier生存分析评估HJURP的预测能力。使用MetaScape和FGSEA进行功能富集分析，并分析空间转录组学和单细胞测序数据以探索HJURP的分布和潜在功能。此外，评估了HJURP表达与基因改变、免疫细胞浸润及潜在治疗反应之间的相关性。
在所有四个队列中，HJURP均被确定为显著的预后生物标志物，高表达与总生存期（OS）死亡风险增加相关（TCGA-LUAD：HR = 1.93，95% CI：1.321 - 2.815，P < 0.001；GSE31210：HR = 2.75，95% CI：1.319 - 5.735，P = 0.007；GSE68465：HR = 1.57，95% CI：1.215 - 2.038，P < 0.001；GSE72094：HR = 2.2，95% CI：1.485 - 3.27，P < 0.001）。功能分析表明，HJURP参与DNA代谢过程、细胞周期调控和有丝分裂过程，与MYC靶点、G2M检查点和DNA修复相关的通路有显著激活。HJURP高表达与TP53、CSMD3、TTN和MUC16的较高突变频率相关，且与促炎性免疫细胞浸润以及包括PD-L1和PD-L2在内的多个免疫检查点呈正相关。预测吉非替尼和索拉非尼等化疗药物对高HJURP表达的肿瘤有效。
HJURP是LUAD的关键生物标志物，始终与不良预后和疾病晚期相关。其高表达与特定的基因改变和免疫特征相关，凸显了其作为治疗靶点的潜力。未来研究应在更大队列中验证这些发现。
