通过多项式逻辑回归分析发现肝细胞癌的基因表达特征和诊断生物标记物

IF 4.1 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of biotechnology Pub Date : 2024-09-06 DOI:10.1016/j.jbiotec.2024.09.003
Ilkyu Park , Hyo-Bin Lee , Nakyoung Kim , Sugi Lee , Kunhyang Park , Mi-Young Son , Hyun-Soo Cho , Dae-Soo Kim
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引用次数: 0

摘要

肝细胞癌(HCC)是全球癌症死亡的主要原因之一,对HCC的发展阶段进行分类有助于早期预后和治疗。这项研究的目的是研究HCC进展过程中的诊断和预后分子特征,包括肿瘤的发生和生长,并根据基因表达水平对其发展阶段进行分类。我们整合了两个癌症系统的数据,包括78例埃德蒙森-斯坦纳(ES)分级患者和417例TNM分期癌症患者。我们使用已识别的特征进行了功能分析。通过多项式逻辑回归模型(MLR),我们对对照组、早期 HCC 和晚期 HCC 进行了分类。该模型在由 45 名患者(肿瘤分期)、394 名患者(ES 分级)和 466 名患者(TNM 分期)组成的三个独立队列中进行了验证。采用多变量 Cox 回归预测 HCC 预后。我们发现 35 个基因在 HCC 进展过程中在 ES 分级和 TNM 分期患者中逐渐上调或下调。这些基因参与细胞分裂、染色体分离和有丝分裂期细胞分裂,通过有丝分裂细胞周期促进肿瘤细胞增殖。MLR 模型在多个癌症系统中准确地区分了对照组、早期 HCC 和晚期 HCC,并在多个独立队列中得到了进一步验证。生存分析表明,TNM 分期的五个基因(HR:3.27,p < 0.0001)和 ES 分级的三个基因(HR:7.56,p < 0.0001)与 HCC 预后有显著相关性。所发现的分子特征不仅能启动肿瘤发生,还能促进 HCC 的发展。它有望改善 HCC 的临床诊断、预后和治疗干预。这项研究加深了我们对 HCC 进展的了解,并为精准医疗方法提供了宝贵的见解。
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Uncovering gene expression signatures and diagnostic – Biomarkers in hepatocellular carcinoma through multinomial logistic regression analysis

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide, and classifying the developmental stages of HCC can help with early prognosis and treatment. This study aimed to investigate diagnostic and prognostic molecular signatures underlying the progression of HCC, including tumor initiation and growth, and to classify its developmental stages based on gene expression levels. We integrated data from two cancer systems, including 78 patients with Edmondson-Steiner (ES) grade and 417 patients with TNM stage cancer. Functional profiling was performed using identified signatures. Using a multinomial logistic regression model (MLR), we classified controls, early-stage HCC, and advanced-stage HCC. The model was validated in three independent cohorts comprising 45 patients (neoplastic stage), 394 patients (ES grade), and 466 patients (TNM stage). Multivariate Cox regression was employed for HCC prognosis prediction. We identified 35 genes with gradual upregulation or downregulation in both ES grade and TNM stage patients during HCC progression. These genes are involved in cell division, chromosome segregation, and mitotic cytokinesis, promoting tumor cell proliferation through the mitotic cell cycle. The MLR model accurately differentiated controls, early-stage HCC, and advanced-stage HCC across multiple cancer systems, which was further validated in various independent cohorts. Survival analysis revealed a subset of five genes from TNM stage (HR: 3.27, p < 0.0001) and three genes from ES grade (HR: 7.56, p < 0.0001) that showed significant association with HCC prognosis. The identified molecular signature not only initiates tumorigenesis but also promotes HCC development. It has the potential to improve clinical diagnosis, prognosis, and therapeutic interventions for HCC. This study enhances our understanding of HCC progression and provides valuable insights for precision medicine approaches.

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来源期刊
Journal of biotechnology
Journal of biotechnology 工程技术-生物工程与应用微生物
CiteScore
8.90
自引率
2.40%
发文量
190
审稿时长
45 days
期刊介绍: The Journal of Biotechnology has an open access mirror journal, the Journal of Biotechnology: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. The Journal provides a medium for the rapid publication of both full-length articles and short communications on novel and innovative aspects of biotechnology. The Journal will accept papers ranging from genetic or molecular biological positions to those covering biochemical, chemical or bioprocess engineering aspects as well as computer application of new software concepts, provided that in each case the material is directly relevant to biotechnological systems. Papers presenting information of a multidisciplinary nature that would not be suitable for publication in a journal devoted to a single discipline, are particularly welcome.
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