Chen Long, Zeng Chong, Yan Limei, Liao Wanyu, Zhen Chen, Yao Jie
Department of Laboratory Medicine and Medical Research Center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, Guangdong 528308, P.R. China.
Department of Pathology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, Guangdong 528308, P.R. China.
Oncol Lett. 2022 May 27;24(1):232. doi: 10.3892/ol.2022.13353. eCollection 2022 Jul.
Lung adenocarcinoma (LUAD) is a disease with high morbidity and mortality rates globally. Holliday junction-recognizing protein (HJURP) has recently been shown to be a potentially useful biomarker for diagnosing and determining the progression and prognosis of different cancer types. The present study assessed the prognostic value of HJURP expression in LUAD and investigated the biological pathways related to HJURP that are involved in LUAD pathogenesis. It was found that high HJURP expression was significantly associated with stage (P=0.001), T grade (P=0.012) and N grade (P=0.012). Overall survival analysis demonstrated that patients with LUAD and high HJURP expression had a worse prognosis compared with those patients with low HJURP expression (P<0.001). Multivariate analysis using the Cox proportional hazards model indicated that the expression of HJURP [hazard ratio (HR), 1.32; 95% confidence interval (CI), 1.09-1.60; P=0.004] and stage (HR, 1.90; 95% CI, 1.19-3.03; P=0.007) were independent prognostic factors for patients with LUAD. Gene set enrichment analysis results showed that genes involved with 'basal transcription factors', the 'cell cycle', 'homologous recombination', 'non-small cell lung cancer' (NSCLC), 'oocyte meiosis', 'p53 signaling pathway', 'pathways in cancer', 'RNA degradation' and 'spliceosome' were differentially enriched in the high HJURP expression phenotype. Significant correlations were also found between HJURP and several tumor-infiltrating immune cells, immunomodulators and immune subtypes. Furthermore, western blotting and qPCR analyses confirmed that HJURP was significantly increased in cell lines of NSCLC. In summary, HJURP may be a potentially useful prognostic molecular biomarker of a poor prognosis in LUAD cases. Further experiments are needed to demonstrate the biological effects of HJURP.
肺腺癌（LUAD）是一种在全球范围内发病率和死亡率都很高的疾病。假日连接识别蛋白（HJURP）最近已被证明是一种潜在的有用生物标志物，可用于诊断以及确定不同癌症类型的进展和预后。本研究评估了HJURP表达在LUAD中的预后价值，并研究了与HJURP相关的、参与LUAD发病机制的生物学途径。研究发现，HJURP高表达与分期（P = 0.001）、T分级（P = 0.012）和N分级（P = 0.012）显著相关。总生存分析表明，与HJURP低表达的LUAD患者相比，HJURP高表达的患者预后更差（P < 0.001）。使用Cox比例风险模型进行的多变量分析表明，HJURP的表达[风险比（HR），1.32；95%置信区间（CI），1.09 - 1.60；P = 0.004]和分期（HR，1.90；95%CI，1.19 - 3.03；P = 0.007）是LUAD患者的独立预后因素。基因集富集分析结果显示，与“基础转录因子”、“细胞周期”、“同源重组”、“非小细胞肺癌”（NSCLC）、“卵母细胞减数分裂”、“p53信号通路”、“癌症中的途径”、“RNA降解”和“剪接体”相关的基因在HJURP高表达表型中差异富集。在HJURP与几种肿瘤浸润免疫细胞、免疫调节剂和免疫亚型之间也发现了显著相关性。此外，蛋白质免疫印迹和qPCR分析证实，HJURP在NSCLC细胞系中显著增加。总之，HJURP可能是LUAD病例中预后不良的一种潜在有用的预后分子生物标志物。需要进一步的实验来证明HJURP的生物学效应。
